Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| Grant Number: 5 UO1 NS32228 |
Not provided
Not provided
Not provided
The Neurologic AIDS Research Consortium Data Safety and Monitoring Board committee recommended to terminate the study early due to futility on 11/6/2009.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Makerere University | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Purpose: The purpose of the study is to assess the safety and effectiveness of minocycline, an antibiotic, in the treatment of Human immunodeficiency virus (HIV)-associated cognitive impairment in Uganda.
Study Design: Treatment, 24-week Randomized, Placebo-Controlled, Double-Blind Phase with Optional 24-week Open Label Phase for Subjects with a cluster of differentiation 4 (CD4) Count in the 251-350 Range
Primary Objective:
· To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline
Secondary Objectives:
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minocycline | Active Comparator | Minocycline 100 mg orally every 12 hours |
|
| Placebo | Placebo Comparator | Placebo minocycline capsules every 12 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| minocycline | Drug | 100 mg capsule every 12 hours by mouth |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) | The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline. | At baseline and week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. | At baseline and week 24 |
| 24-week Change of Karnofsky Performance Score |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ned Sacktor, MD | Johns Hopkins School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Infecious Diseas Institute | Kampala | Uganda |
Total of 353 participants were screened; only 73 were randomized and thus 280 were not enrolled: 146 of them did not have cognitive impairment, 55 of them lacked laboratory inclusion criteria, and 79 of them had "others".
The recruitment period was from Mar 2008 to Oct 2009 when the study was stopped early (Data and Safety Monitoring Board (DSMB) decision based on futility) on Nov 2009. The study participants were recruited from the Infectious Disease Institute, Makerere University, Kampala, Uganda.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Minocycline | Minocycline 100 mg orally every 12 hours |
| FG001 | Placebo | Placebo minocycline capsules every 12 hours |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Step1 |
|
| |||||||||||||||||||||
| Step2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Minocycline | Minocycline 100 mg orally every 12 hours |
| BG001 | Placebo | Placebo minocycline capsules every 12 hours |
| 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 |
| 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 | 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) | The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of norm-adjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24 - U NP Sum at baseline. | The descriptive statistics are based on per protocol analysis. For the statistical analysis, ITT analysis was used and the missing U NP Sums at week 24 were imputed using a multiple regression imputation method. The number of participants analyzed for the ITT analysis was 73 (36 for Minocycline and 37 for Placebo). | Posted | Mean | Standard Deviation | z-score | At baseline and week 24 |
|
48 weeks
The lab assessments were conducted at weeks 0, 12, 24, and 48.
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 | Minocycline 100 mg orally every 12 hours |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Infections and infestations | Appendix 76 | Systematic Assessment | The patient died due to Pulmonary Tuberculosis. The cause of death was unrelated to the study treatment as she was not on the study treatment at the time of her death. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | General disorders | Appendix 76 | Systematic Assessment |
The estimated sample size was 100; however, due to early termination of the study, the total number of randomized participants was 73.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sachiko Miyahara | Harvard School of Public Health | 617-432-2837 | miyahara@sdac.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| D015526 | AIDS Dementia Complex |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
Not provided
Not provided
| ID | Term |
|---|---|
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| minocycline placebo capsule |
| Drug |
1 capsule every 12 hours by mouth |
|
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
| At baseline and week 24 |
| Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. | Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 |
| Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. | Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks |
| 24-week Change of CD4 Cell Counts | The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm^3. | At baseline and week 24 |
| 48-week Change of CD4 Cell Counts | The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm^3. | At baseline and week 48 |
| 24-week Change of Instrumental Activities of Daily Living | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. | At baseline and week 24 |
| 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) | The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline. | At baseline and week 24 |
| 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score | The outcome is the total CES-D score at week 24 - the total CES-D score at baseline. The total CES-D score is based on 20 CES-D items, such as "I was bothered by things that usually don't bother me" and "I did not feel like eating, my appetite was poor". Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by -1, the total CES-D score is a simple sum of all items. The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms. | At baseline and week 24 |
| Protocol Violation |
|
| Pregnancy |
|
| Withdrawal by Subject |
|
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale | The Memorial Sloan Kettering (MSK) clinical scale was defined below:
| Number | Participants |
|
| Baseline Cluster of Differentiation Four (CD4) Count | Median | Full Range | cells/mm^3 |
|
| Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL)) | Log Mean | Inter-Quartile Range | copies/mL |
|
| Baseline Karnofsky's Performance Score | 100:Normal,90:normal;Minor Signs or Symptoms of Disease,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; Hospitalization Necessary;Active Supportive Treatment is Necessary,10:Moribund, Fatal Processes Progressing Rapidly,0:Death | Number | Participants |
|
| Baseline Instrumental Activities of Daily Living (IADL) | 16 tasks: Housekeeping,Managing Finances,Buying Groceries,Cooking,Planning Social Activities,Understanding Reading Materials/TV,Transportation,Using the Telephone,Home Repairs,Bathing,Dressing,Shopping,Laundry,Taking/Keeping Track of Medication,Child Care,Work. For the baseline IADL measure, participants were given four choices to choose for having difficulty on the 16 tasks:Primarily Cognitive problems,Primarily physical problems,equally cognitive and physical problems,not having any difficulties on previous tasks. | Number | Participants |
|
| Baseline Overall Neurological Assessment | Number | Participants |
|
| Baseline Uganda Neuropsychological Test Battery Summary measure (U NP Sum) | Uganda Neuropsychological Test Battery Summary measure (U NP Sum)is the average z-scores of the 9 neurupsychological tests:Grooved Pegboard Dominant Hand,Grooved Pegboard Non-dominant Hand,Color Trail1,Color Trail2,Symbol Digit,WHO/UCLA Verbal Learning Test Trial 5,WHO/UCLA Verbal Learning Test Delayed Recall,Digit Span-Forward,Digit Span-Backward Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| WHO-UCLA Auditory Verbal Learning Test (AVLT): Trials Total | World Health Organization-University of California Los Angeles (WHO-UCLA) Auditory Verbal Learning Test (AVLT) is a full-scale memory assessment. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| WHO-UCLA Auditory Verbal Learning Test (AVLT): Delayed | World Health Organization-University of California Los Angeles (WHO-UCLA) Auditory Verbal Learning Test (AVLT) is a memory assessment. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Color Trails 1 | The Color Trails tests measure speed of attention, sequencing, mental flexibility, visual search, and motor function. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Color Trails 2 | The Color Trails tests measure speed of attention, sequencing, mental flexibility, visual search, and motor function. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Grooved Pegboard Dominant | 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. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Grooved Pegboard Non-dominant | 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. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Symbol Digit | 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. Maximum score is 110 points. Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Digit Span Backward | Digit span assesses attention, concentration, and mental control(e.g., Repeat the numbers 1-2-3 in reverse sequence). Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
| Digit Span Forward | Digit span assesses attention, concentration, and mental control(e.g., Repeat the numbers 1-2-3 in reverse sequence). Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x - μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms. | Mean | Standard Deviation | z-scores |
|
Minocycline 100 mg orally every 12 hours |
| OG001 | Placebo | Placebo minocycline capsules every 12 hours |
|
|
|
| Secondary | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. | The descriptive statistics were based on observed data. Since all participants reported there were no change in the MSK score at week 24, no statistical test was conducted. | Posted | Number | participants | At baseline and week 24 |
|
|
|
| Secondary | 24-week Change of Karnofsky Performance Score | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. | This analysis includes the participants with Karnofsky performance score at baseline and week 24. | Posted | Number | percentage of participants | At baseline and week 24 |
|
|
|
|
| Secondary | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. | The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. | This analysis includes every randomized participants. A total of 21 minocycline and 20 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 24 weeks | Posted | Number | participants with an event | Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 |
|
|
|
|
| Secondary | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms | The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, life-threatening, or death event. | This analysis includes every randomized participants. A total of 22 minocycline and 21 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 48 weeks. | Posted | Number | participants with an event | Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks |
|
|
|
|
| Secondary | 24-week Change of CD4 Cell Counts | The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm^3. | This analysis used the participants with CD4 cell counts at baseline and week 24. | Posted | Mean | Standard Deviation | cells/mm^3 | At baseline and week 24 |
|
|
|
|
| Secondary | 48-week Change of CD4 Cell Counts | The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm^3. | This analysis used the participants with CD4 cell counts at baseline and week 48. | Posted | Mean | Standard Deviation | cells/mm^3 | At baseline and week 48 |
|
|
|
|
| Secondary | 24-week Change of Instrumental Activities of Daily Living | The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. | The analysis includes participants with IADL scores at baseline and week 24. | Posted | Number | percentage of participants | At baseline and week 24 |
|
|
|
|
| Secondary | 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) | The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline. | The analysis includes participants with HIV RNA viral loads at baseline and week 24. | Posted | Median | Inter-Quartile Range | copies/mL | At baseline and week 24 |
|
|
|
|
| Secondary | 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score | The outcome is the total CES-D score at week 24 - the total CES-D score at baseline. The total CES-D score is based on 20 CES-D items, such as "I was bothered by things that usually don't bother me" and "I did not feel like eating, my appetite was poor". Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by -1, the total CES-D score is a simple sum of all items. The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms. | The analysis includes participants with CES-D scores at baseline and week 24. | Posted | Mean | Standard Deviation | scores on a scale | At baseline and week 24 |
|
|
|
|
| 2 |
| 36 |
| 26 |
| 36 |
| EG001 | Placebo | Placebo minocycline capsules every 12 hours | 1 | 37 | 25 | 37 |
|
| Potassium | Renal and urinary disorders | Appendix 76 | Systematic Assessment | The participant had high potassium level. The value was 7.8 when the normal limit was 5.3. |
|
| Sgpt | Hepatobiliary disorders | Appendix 76 | Systematic Assessment | The lab value was 836 when the normal value was 45. |
|
| Sgot | Hepatobiliary disorders | Appendix 76 | Systematic Assessment | The lab value was 901 when the normal value was 40. |
|
| Allergic Rash | Skin and subcutaneous tissue disorders | Appendix 76 | Systematic Assessment |
|
| Carbon Dioxide | General disorders | Appendix 76 | Systematic Assessment |
|
| Phosphorus | Renal and urinary disorders | Appendix 76 | Systematic Assessment |
|
| Sodium | Renal and urinary disorders | Appendix 76 | Systematic Assessment |
|
| Absolute Neutrophil Count | Blood and lymphatic system disorders | Appendix 76 | Systematic Assessment |
|
| SGOT | Hepatobiliary disorders | Appendix 76 | Systematic Assessment |
|
| White Blood Cells | Blood and lymphatic system disorders | Appendix 76 | Systematic Assessment |
|
Not provided
Not provided
| 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 |
| D012897 | Slow Virus Diseases |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| 12.01 - 24 weeks |
|
| 12.01-24 weeks |
|
| 24.01-48 weeks |
|