Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1U01AI068636 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
This study was terminated early due to futility.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| Neurologic AIDS Research Consortium (NARC) | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.
Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.
This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.
There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Minocycline | Experimental | 100 mg orally every 12 hours |
|
| Arm 2: Matching placebo | Placebo Comparator | orally every 12 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | Tetracycline antibiotic, 100 mg taken orally every 12 hours |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cognitive Performance Compared to Baseline | Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:
| At baseline and week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Global Deficit Z-Score (GDS) | GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ned Sacktor, MD | Department of Neurology, Johns Hopkins Bayview Medical Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA-David Geffen School of Medicine | Los Angeles | California | 90035 | United States | ||
| University of California |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15569045 | Background | Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. doi: 10.1111/j.1365-2559.2004.02004.x. | |
| 16471077 | Background | Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, Temesgen Z. Human immunodeficiency virus-associated peripheral neuropathies. Mayo Clin Proc. 2006 Feb;81(2):213-9. doi: 10.4065/81.2.213. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Minocycline | 100 mg orally every 12 hours |
| FG001 | Matching Placebo | Placebo taken orally every 12 hours |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Step 1: Minocycline vs. Placebo |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo (Tetracycline) |
| Drug |
Tetracycline antibiotic placebo, orally every 12 hours |
|
| At baseline and week 24 |
| Change in Investigator's Clinical Global Impression Score (ICGIS) | Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening. For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved. | At week 24 |
| Change in Cognitive Gross Motor Function Domain Z-Score | The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline). | At baseline and week 24 |
| Change in Fine Motor Function Domain Z-Score | The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline). | At baseline and week 24 |
| Change in Psychomotor Function Domain Z-Score | The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline). | At baseline and week 24 |
| Change in Fine Motor/Nonverbal Function Domain Z-Score | The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline). | At baseline and week 24 |
| Change in Information Processing Function Domain Z-Score | The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline). | At baseline and week 24 |
| Change in Verbal Memory Domain Z-Score | The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline). | At baseline and week 24 |
| Change in Frontal Systems Function Domain Z-Score | The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline). | At baseline and week 24 |
| Change in Karnofsky Performance Score | The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks. For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created. | At baseline and week 24 |
| Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) | The outcome was the 24 week change in CD4 cell count (week 24-baseline). | At baseline and weeks 24 |
| Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) | The outcome was the 24 week change of CD8 cell counts (week 24-baseline). | At baseline and week 24 |
| Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section. | Throughout study up to week 48 |
| Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL). | At baseline and week 24 |
| Changes in Instrumental Activities of Daily Living Questionnaire | The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline. | At baseline and week 24 |
| Changes in Medication Management Test (Modified) | The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management. | At baseline and weeks 24 |
| Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Protein marker of oxidative stress (Ceramides, Monohexosylceramides, Dihydro Glycosyl Galceramides, and Dihexosylceramides). For all markers, the outcome is the 24 week change (week 24-baseline). | At pre-entry and Week 24 |
| Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Protein markers of oxidative stress (Protein carbonyls) and markers of immune activation (TNF-a, IL-6,CXCL8, Hepatocyte growth factor, Osteopontin, sFAS, sFAS ligand, and CXCL12). For all markers, the outcome is the 24 week change (week 24-baseline). | At pre-entry and Week 24 |
| Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only) | Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline). | At pre-entry and Week 24 |
| Changes in Neurotransmitter Levels (Unit = uM Only) | Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline). | At pre-entry and Week 24 |
| Changes in Alternate Psychomotor Function Z-Score | The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline). | At baseline and week 24 |
| Changes in Alternate Verbal Memory Z-Score | The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline). | At baseline and week 24 |
| Changes in Alternate Frontal Systems Z-Score | The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline). | At baseline and week 24 |
| San Diego |
| California |
| 92103 |
| United States |
| University of Colorado Health Science Center | Denver | Colorado | 80262-3706 | United States |
| The Ponce de Leon Ctr. CRS | Atlanta | Georgia | 30308 | United States |
| Northwestern University CRS | Chicago | Illinois | 60611 | United States |
| Johns Hopkins School of Medicine | Baltimore | Maryland | 21287-8106 | United States |
| Massachusetts General Hospital, Division of Infectious Diseases | Boston | Massachusetts | 02114 | United States |
| Henry Ford Hosp. CRS | Detroit | Michigan | 48202 | United States |
| Washington University | St Louis | Missouri | 63108-2138 | United States |
| NYU Med Ctr, Dept of Medicine | New York | New York | 10016 | United States |
| 1101 University of Rochester Medical Center, Division of Infectious Diseases | Rochester | New York | 14642 | United States |
| University of North Carolina, AIDS Clinical Trials Unit | Chapel Hill | North Carolina | 27514 | United States |
| The Research and Education Group - Portland CRS | Portland | Oregon | 97209 | United States |
| University of Pennsylvania, ACTU | Philadelphia | Pennsylvania | 19104 | United States |
| Virginia Commonwealth Univ. Medical Ctr. CRS | Richmond | Virginia | 23219 | United States |
| Univ of Washington, Harborview Medical Ctr | Seattle | Washington | 98104 | United States |
| 15855434 | Background | Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA. 2005 Apr 27;293(16):2003-11. doi: 10.1001/jama.293.16.2003. |
| 21900636 | Result | Sacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen BA, Paul R, Robertson K, Jarocki B, Scarsi K, Coombs RW, Zink MC, Nath A, Smith E, Ellis RJ, Singer E, Weihe J, McCarthy S, Hosey L, Clifford DB; ACTG A5235 team. Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial. Neurology. 2011 Sep 20;77(12):1135-42. doi: 10.1212/WNL.0b013e31822f0412. Epub 2011 Sep 7. |
| 25377444 | Result | Sacktor N, Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL, Graham D, Zink MC, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D; ACTG A5235 team. Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment. J Neurovirol. 2014 Dec;20(6):620-6. doi: 10.1007/s13365-014-0292-0. Epub 2014 Nov 7. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Step 2: Minocycline(Open Label) for All |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Minocycline | 100 mg orally every 12 hours |
| BG001 | Matching Placebo | Placebo taken orally every 12 hours |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Cognitive Performance Score NPZ-8 | Cognitive performance is measured by NPZ-8. The NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery:
| Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Global Deficit Z-Score (GDS) | GDS is defined as the average of age and education adjusted z-scores of 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Cognitive Gross Motor Function Domain Z-Score | The cognitive gross motor function is age and education adjusted z-score of Timed Gait. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Fine Motor Function Domain Z-Score | This is an average z-scores of Grooved Pegboard Dominant and Non-Dominant Hand Tests adjusted for age, sex, education, and African-American ethnicity. The grooved pegboard is a manipulative dexterity test requiring rapid visual-motor coordination. The test is completed using the dominant hand (GPD) and then using the non-dominant hand (GPN). The score for each hand is the time in seconds that the participant takes to complete the entire board. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Psychomotor Function Domain Z-Score | This is an average of z-scores of Trail Making Part A (TMA) and Trail Making Part B (TMB) tests adjusted for age, sex, education, and African-American ethnicity. The TMA and TMB tests are measures of planning ability, visual-motor speed and concentration. Subjects are required to connect randomly placed numbers in sequence (1-25 for TMA) or to sequentially connect both numbers and letters while alternating back and forth (1-A-2-B-3-C-4-D etc. for TMB). Scores are the time in seconds required to complete the tasks. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Fine Motor/Nonverbal Function Domain Z-Score | This score is a age and education adjusted z score of Symbol Digit Test (SYD). This test assesses the participant's ability to maintain rapid visual-motor sequencing in a timed test. The score is the total number of correctly transcribed numbers in the time limit (90 seconds). Participants receive 1 point for each item filled in correctly. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Information Processing Function Domain Z-Score | This is the average age and education adjusted z-scores of simple and sequential reaction time tests adjusted for age and education. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Verbal Memory Domain Z-Score | This is the average of z-scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall Tests adjusted for age and education. The recognition test list comprises 24 words, consisting of 12 words from the original list and 12 "distracters". The subject must answer "yes" if the word was from the list and "no" otherwise. Twenty minutes after the third list from verbal learning and immediate recall, delayed recall is assessed by asking the subject to recall as many words as possible from the list. The score is the number of words that are correctly recalled from the original list. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Frontal Systems Function Domain Z-Score | This is the average age and education adjusted z-scores of Stroop Color Interference Test (CTP) and interference task (STP). The Stroop Task is a measure of divided attentional abilities. Performance is measured by the amount of time required to read each of three cards: (1) blocks of colors, (2) names of colors, and (3) colored words. For each task, the time (in seconds) is the score that should be recorded on the form. A task that cannot be completed in 240 seconds is scored as incomplete. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Karnofsky Score | Karnofsky performance score is ranged from 100 to 0: 100: Normal; 90: Able to Carry on normal Activity; 80: Normal Activity with Effort; Some Signs or Symptoms of Disease; 70: Cares for Self, Unable to Carry on Normal Activity or to Do Active Work; 60: Requires Occasional Assistance but is Able to Care for Most of Needs; 50: Requires Considerable Assistance and Frequent Medical Care; 40: Disabled, Requires Special Care and Assistance; 30: Severely Disabled; Hospitalization Indicated Although Death is Not Imminent; 20: Very Sick; 10: Morbibund, Fatal Processes Progressing Rapidly; 0: Death | Number | participants |
| |||||||||||||||||
| Cluster of Differentiation 4 (CD4) | CD4 counts by group at baseline | Mean | Standard Deviation | copies/mm^3 |
| ||||||||||||||||
| Cluster of Differentiation 8 (CD8) | CD8 counts by group at baseline | Mean | Standard Deviation | copies/mm^3 |
| ||||||||||||||||
| HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads | HIV Plasma RNA viral load less than 30 copies/mL is undetectable, the values will be imputed as 30 copies/mL. | Number | participants |
| |||||||||||||||||
| HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL) | HIV CSF RNA viral load less than 30 copies/mL is undetectable, the values will be imputed as 30 copies/mL. | Number | participants |
| |||||||||||||||||
| Central Nervous System (CNS) Penetration Score | The baseline CNS penetration score is calculated based on the revised CNS penetration-effectiveness ranks (provided by Dr. Scott Letendre). The score is simply a sum of the ranks of all drugs which participants took at baseline. The better the drug penetrates, the higher the score. The range of ranks are 1 to 4, so the CNS penetration score is integer numbers greater than 1. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||||
| Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline | Participants were stratified based on two factors. One is CSF HIV-1 RNA. This variable has three levels using the TaqMan assay in CSF: (1) HIV CSF RNA VLs ≥30 copies/mL (detectable), <30 copies/mL (Undetectable), or no lumbar punctures (LPs). The assessment was conducted BEFORE the baseline in order to use this information for randomization. | Number | participants |
| |||||||||||||||||
| Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline | The 2nd stratification factor is progressive neurocognitive decline defined by objective or subjective criteria at pre-baseline. A decline of at least 1.0 standard deviation below age-matched and education-matched controls on two or more independent tests or 2.0 standard deviations below age-matched and education-matched controls on one test within 1 year before entry is defined as objective decline. Otherwise, subjective neurocognitive decline is defined by the participant or family member or caregiver AND a Center for Epidemiological Studies Depression score <16 within 45 days before entry. | Number | participants |
| |||||||||||||||||
| Instrumental Activities of Daily Living (IADL) Summary Score | The IADL questionnaire has 16 common tasks: 1. Housekeeping; 2.Managing Finances; 3. Buying Groceries; 4.Cooking; 5. Planning Social Activities; 6.Understanding Reading Materials/TV; 7.Transportation; 8.Using the Telephone; 9.Home Repairs; 10.Bathing; 11.Dressing; 12.Shopping; 13.Laundry; 14.Taking/Keeping Track of Medication; 15.Child Care; 16.Work. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given; otherwise 0. The IADL score is a sum of 16 indicators divided by 16. The lower score indicates better. The range is from 0 to 1. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||||
| Medication Management Test (MMT) Score | The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. | Mean | Standard Deviation | Scores on a scale |
| ||||||||||||||||
| Alternate Psychomotor Function Z-Score | This is the average of z scores of Trail Making Part A and Symbol Digit Tests. Trail Making Part A z score was adjusted for age, sex, education, and African-Ametrican ethnicity. Symbol Digit z score was adjusted for age and education. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Alternate Verbal Memory Z-Score | This is the average of age and education adjusted z scores of standardized trials 1 to 3 and delayed recall tests. | Mean | Standard Deviation | z-score |
| ||||||||||||||||
| Alternate Frontal Systems Z-Score | This is average of z scores of standardized interference task and trailmaking part b tests. The interference task z score was adjusted for age and education. The trailmaking part b z score was adjusted for age, sex, education, and African-American ethnicity. | Mean | Standard Deviation | z-score |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Cognitive Performance Compared to Baseline | Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:
| The descriptive statistics above were based on the observed data; however, the statistical analysis was conducted by the ITT analysis and the missing outcomes at week 24 were imputed based on multiple regression imputations. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Global Deficit Z-Score (GDS) | GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline). | The analysis was based on the observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Investigator's Clinical Global Impression Score (ICGIS) | Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening. For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved. | The analysis was based on observed data. | Posted | Number | participants | At week 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Cognitive Gross Motor Function Domain Z-Score | The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline). | The analysis was based on the observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Fine Motor Function Domain Z-Score | The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Psychomotor Function Domain Z-Score | The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Fine Motor/Nonverbal Function Domain Z-Score | The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Information Processing Function Domain Z-Score | The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Verbal Memory Domain Z-Score | The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Frontal Systems Function Domain Z-Score | The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Karnofsky Performance Score | The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks. For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created. | The analysis was based on observed data. | Posted | Number | participants | At baseline and week 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) | The outcome was the 24 week change in CD4 cell count (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | cells/mm^3 | At baseline and weeks 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) | The outcome was the 24 week change of CD8 cell counts (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | cells/mm^3 | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section. | The analysis includes all randomized participants. A total of 37 minocycline and 38 placebo participants reported Grade 2 or higher toxicity and/or signs and symptoms during 48 weeks. | Posted | Number | participants with an event | Throughout study up to week 48 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL). | The summary statistics were based on observed data. No statistical analysis was conducted. | Posted | Number | participants | At baseline and week 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Instrumental Activities of Daily Living Questionnaire | The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline. | The analysis was based on observed data. | Posted | Number | participants | At baseline and week 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Medication Management Test (Modified) | The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management. | The analysis was based on observed data. | Posted | Mean | Standard Deviation | scores on a scale | At baseline and weeks 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Protein marker of oxidative stress (Ceramides, Monohexosylceramides, Dihydro Glycosyl Galceramides, and Dihexosylceramides). For all markers, the outcome is the 24 week change (week 24-baseline). | Participants who were willing to receive the lumber punctures at week 0 and 24. | Posted | Median | Inter-Quartile Range | counts per second | At pre-entry and Week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Protein markers of oxidative stress (Protein carbonyls) and markers of immune activation (TNF-a, IL-6,CXCL8, Hepatocyte growth factor, Osteopontin, sFAS, sFAS ligand, and CXCL12). For all markers, the outcome is the 24 week change (week 24-baseline). | Participants who were willing to receive the lumber punctures at week 0 and 24. | Posted | Median | Inter-Quartile Range | pg/mL | At pre-entry and Week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only) | Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline). | Participants who were willing to receive the lumber punctures at week 0 and 24. | Posted | Median | Inter-Quartile Range | Pixels/mm^2 | At pre-entry and Week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Neurotransmitter Levels (Unit = uM Only) | Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline). | Participants who were willing to receive the lumber punctures at week 0 and 24. | Posted | Median | Inter-Quartile Range | uM | At pre-entry and Week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Alternate Psychomotor Function Z-Score | The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline). | The analysis was based on the observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Alternate Verbal Memory Z-Score | The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline). | The analysis is based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Alternate Frontal Systems Z-Score | The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline). | The analysis was based on observed data. | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
|
Up to 48 weeks since the randomization.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Minocycline | 100 mg orally every 12 hours | 7 | 52 | 18 | 52 | ||
| EG001 | Matching Placebo | Placebo taken orally every 12 hours | 3 | 55 | 34 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood amylase increased | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment | Grade 4: Life-threatening |
|
| Vocal cord paralysis | Nervous system disorders | MedDRA 13.1 | Systematic Assessment | Amyotrophic lateral sclerosis (ALS) |
|
| Renal failure | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment | Requires dialysis |
|
| Basal cell carcinoma | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment | On nose |
|
| Tooth infection | General disorders | MedDRA 13.1 | Systematic Assessment | Tooth discoloration |
|
| Suicidal ideation | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment | Resulted in hospitalization |
|
| Suicidal attempt | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment | By medication overdose |
|
| Hypertension | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Blood triglycerides increased | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Sob | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Diarrhea/Loose | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Headache | General disorders | MedDRA 13.1 | Systematic Assessment |
|
Originally, 100 participants were expected to enroll. As of the early termination notice, 107 participants were randomized, yet not all subjects could complete the 24 week assessment.
In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, Inc. | (301) 628-3313 | ACTGCT.Gov@s-3.com |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008911 | Minocycline |
| D013752 | Tetracycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| 80 |
|
| 90 |
|
| 100 |
|
| missing |
|
| Plasma RNA VL < 30 copies/mL |
|
| missing |
|
| CSF RNA VL <30 copies/mL |
|
| missing |
|
| CSF RNA VL >= 30 copies/mL |
|
| No Lumbar Punctures (LPs) |
|
| Subjective NP Test |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|