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Cognitively normal individuals, patients with Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD) will undergo clinical screening, neuropsychological tests, blood and urine analyses, quantitative magnetic resonance imaging (MRI) and proton (1H ) and carbon 13 (13C) magnetic resonance spectroscopy (MRS). Each individual will receive minocycline oral administration for 4 weeks initially, after which MRI, MRS and neuropsychological results will be recorded. If no adverse side effects occur, subjects will continue minocycline administration for an additional 5 months.
In the course of on-going trials of novel MRI procedures for Neurological Diagnosis, the investigators have established non-invasive BIOMARKERS (Note: Biomarkers are objective Laboratory tests used in, but not replacing Clinical diagnostic criteria of any disease,in this case age-related dementia of the Alzheimer type and its pre-clinical forms including Mild Cognitive Impairment - MCI) which significantly assist in the Diagnosis of Alzheimer's Disease. MRS, rather like blood tests which are applied for screening and exclusion of medical disorders, provides a pattern of brain chemicals from which this and many other diagnoses have become available (see: Magnetic Resonance Spectroscopy in Neurological Diagnosis: E.R Danielsen and B.D. Ross, Marcel Dekker New York, 1999). Diagnosis of Alzheimer's Disease has hitherto been exclusively a clinical diagnosis, made on the basis of non-specific tests by the treating physician/neurologist. Furthermore, treatments have been of limited efficacy so that the pressure for conclusive diagnosis or an objective characterization of disease progression (or better, regression) has not been a priority. This conservative approach to Alzheimer's Disease changed in 2010 with the Report of National Institutes of Aging. First: The failures of treatment have been ascribed to introduction only in patients with advanced disease ("dementia"). Second: A preliminary form of AD, known as pre-clinical or Mild Cognitive Impairment, has been recognized, distinct from, and generally earlier in the disease course. Third: A new set of diagnostic criteria, which include objective 'biomarkers', from cerebrospinal fluid, genetic and imaging analyzes, has been accepted by the Expert Panel. Finally, Clinical trials of existing and new drugs for Alzheimer's Disease are expected to yield better results if initiated earlier - in the pre-clinical phase - and the outcomes evaluated by the earlier changes in an approved panel of biomarkers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minocycline | Active Comparator | Subjects will be administered 50mg minocycline twice daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | 50mg, twice daily for 6 months. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial skills. RBANS was developed as a stand-alone "core" battery for the detection and neurocognitive characterization of dementia and as a brief neurocognitive battery for the detection and tracking of neurocognitive deficits in a variety of disorders. (Reference: http://rbans.com/) Qualitative Description of Index Scores: Index Score Classification 130 and above Very Superior 120-129 Superior 110-119 High Average 90-109 Average 80-89 Low Average 70-79 Borderline 69 and below Extremely Low Psychometric range for RBANS: AD 0 - 77 MCI 78 - 99 Normal > 100 Range of scores: Minimum = 0, Maximum = 130 Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
| Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC). | Using magnetic resonance images acquired, hippocampal volume was measured monthly for 6 months. Normal range for hippocampal volume in aged-matched controls is 6.6 - 8.8 cm^3. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
| Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC) | It has been demonstrated in numerous studies over the past decade that magnetic resonance spectroscopy (MRS) can be used for the diagnosis of Alzheimer's disease. By measuring an area within the posterior cingulate gyrus, one can obtain a biochemical signature of that region in AD whereby NAA is reduced and mI is increased. These two biomarkers, N-acetylaspartate (NAA, a neuronal marker) and myo-inositol (mI, a glial marker) were quantified and then used to calculate NAA/mI (an index currently widely used for AD and MCI diagnosis). Scale of MRS biomarkers for aged-matched controls: NAA = 1.43, mI = 0.60, NAA/mI = 2.38. Any value lower than NAA/mI of 2.38 are considered not normal. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian D Ross | Huntington Medical Research Institutes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huntington Medical Research Institutes | Pasadena | California | 91105 | United States |
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| Label | URL |
|---|---|
| Related Info | View source |
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Patients were recruited from local physicians, through Clinical Trials website and the AD association.
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| ID | Title | Description |
|---|---|---|
| FG000 | Minocycline | Subjects were administered 50mg minocycline twice daily for 6 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Minocycline | Subjects administered 50mg minocycline twice daily for 6 months |
| 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 | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial skills. RBANS was developed as a stand-alone "core" battery for the detection and neurocognitive characterization of dementia and as a brief neurocognitive battery for the detection and tracking of neurocognitive deficits in a variety of disorders. (Reference: http://rbans.com/) Qualitative Description of Index Scores: Index Score Classification 130 and above Very Superior 120-129 Superior 110-119 High Average 90-109 Average 80-89 Low Average 70-79 Borderline 69 and below Extremely Low Psychometric range for RBANS: AD 0 - 77 MCI 78 - 99 Normal > 100 Range of scores: Minimum = 0, Maximum = 130 Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. | Mean | Standard Deviation | units on a scale | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
|
7 months
No adverse events were reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Minocycline | No adverse events were reported in any subjects who were taking minocycline. All subjects underwent monthly blood tests to monitor alanine transaminase and blood urea nitrogen levels. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principal Investigator | Huntington Medical Research Institutes | 6263975840 | mrs@hmri.org |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| D000090862 | Neuroinflammatory Diseases |
| C562573 | cyclopia sequence |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| D013752 | Tetracycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Minocycline AD |
Alzheimer subjects who were administered 50mg minocycline twice daily. |
| OG001 | Minocycline MCI | Mild cognitively impaired subject who was administered 50mg minocycline twice daily. |
| OG002 | Minocycline NC | Normal control subjects who were administered 50mg minocycline twice daily. |
|
|
| Primary | Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC). | Using magnetic resonance images acquired, hippocampal volume was measured monthly for 6 months. Normal range for hippocampal volume in aged-matched controls is 6.6 - 8.8 cm^3. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. | Mean | Standard Deviation | cm^3 | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
|
|
|
| Primary | Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC) | It has been demonstrated in numerous studies over the past decade that magnetic resonance spectroscopy (MRS) can be used for the diagnosis of Alzheimer's disease. By measuring an area within the posterior cingulate gyrus, one can obtain a biochemical signature of that region in AD whereby NAA is reduced and mI is increased. These two biomarkers, N-acetylaspartate (NAA, a neuronal marker) and myo-inositol (mI, a glial marker) were quantified and then used to calculate NAA/mI (an index currently widely used for AD and MCI diagnosis). Scale of MRS biomarkers for aged-matched controls: NAA = 1.43, mI = 0.60, NAA/mI = 2.38. Any value lower than NAA/mI of 2.38 are considered not normal. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration. | Mean | Standard Deviation | Ratio | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
|
| Averaged Values for Months 4-6 |
|
|
| Averaged Values for Months 4-6 |
|