Minocycline in Patients With Alzheimer's Disease
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Minocycline Subjects will be administered 50mg minocycline twice daily. |
Drug: Minocycline
50mg, twice daily for 6 months.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)]
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.
- Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC). [Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)]
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.
- Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC) [Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Cognitively normal elderly subjects between the ages of 55-90 and patients aged 55 - 90 years who have mild cognitive impairment (MCI) or clinically defined Alzheimer's disease.
Exclusion Criteria:
-
Any person with medical devices such as cardiac pacemakers/defibrillators or neuro-implants as they are contra-indications for MRI/MRS exam.
-
Since the effects of MRI are unknown to the fetus or unborn child, any person who is or may be pregnant will be excluded from the study.
-
History of known allergy or intolerance to minocycline or any other tetracycline
-
Impaired renal function (plasma Creatinine) or blood urea nitrogen (BUN) levels exceeds twice normal upper limit which can result in higher serum levels of tetracycline, azotemia, hyperphosphatemia and acidosis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Huntington Medical Research Institutes | Pasadena | California | United States | 91105 |
Sponsors and Collaborators
- Huntington Medical Research Institutes
Investigators
- Principal Investigator: Brian D Ross, Huntington Medical Research Institutes
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- LKW-AB34
Study Results
Participant Flow
| Recruitment Details | Patients were recruited from local physicians, through Clinical Trials website and the AD association. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Minocycline |
|---|---|
| Arm/Group Description | Subjects were administered 50mg minocycline twice daily for 6 months |
| Period Title: Overall Study | |
| STARTED | 13 |
| COMPLETED | 13 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Minocycline |
|---|---|
| Arm/Group Description | Subjects administered 50mg minocycline twice daily for 6 months |
| Overall Participants | 13 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
4
30.8%
|
| >=65 years |
9
69.2%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
73.5
(8.8)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
38.5%
|
| Male |
8
61.5%
|
| Region of Enrollment (participants) [Number] | |
| United States |
13
100%
|
Outcome Measures
| Title | Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) |
|---|---|
| Description | 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. |
| Time Frame | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Minocycline AD | Minocycline MCI | Minocycline NC |
|---|---|---|---|
| Arm/Group Description | Alzheimer subjects who were administered 50mg minocycline twice daily. | Mild cognitively impaired subject who was administered 50mg minocycline twice daily. | Normal control subjects who were administered 50mg minocycline twice daily. |
| Measure Participants | 4 | 1 | 8 |
| Baseline Values |
49
(8)
|
81
|
106
(13)
|
| Averaged Values for Months 1-3 |
32.5
(3.4)
|
58.7
|
108.4
(26)
|
| Averaged Values for Months 4-6 |
32.9
(4.2)
|
63.8
|
123.6
(37.1)
|
| Title | Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC). |
|---|---|
| Description | 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. |
| Time Frame | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Minocycline AD | Minocycline MCI | Minocycline NC |
|---|---|---|---|
| Arm/Group Description | Alzheimer subjects who were administered 50mg minocycline twice daily. | Mild cognitively impaired subject who was administered 50mg minocycline twice daily. | Normal control subjects who were administered 50mg minocycline twice daily. |
| Measure Participants | 4 | 1 | 8 |
| Baseline Values |
5.49
(1.14)
|
6.35
|
6.98
(1.18)
|
| Averaged Values for Months 1-3 |
5.42
(1.06)
|
6.30
|
6.92
(0.48)
|
| Averaged Values for Months 4-6 |
4.94
(1.2)
|
7.60
|
6.82
(0.45)
|
| Title | Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC) |
|---|---|
| Description | 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. |
| Time Frame | Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Minocycline AD | Minocycline MCI | Minocycline NC |
|---|---|---|---|
| Arm/Group Description | Alzheimer subjects who were administered 50mg minocycline twice daily. | Mild cognitively impaired subject who was administered 50mg minocycline twice daily. | Normal control subjects who were administered 50mg minocycline twice daily. |
| Measure Participants | 4 | 1 | 8 |
| Baseline Values |
1.69
(0.38)
|
1.87
|
2.42
(0.08)
|
| Averaged Values for Months 1-3 |
1.78
(0.61)
|
1.80
|
2.44
(0.26)
|
| Averaged Values for Months 4-6 |
1.84
(0.61)
|
2.08
|
2.47
(0.41)
|
Adverse Events
| Time Frame | 7 months | |
|---|---|---|
| Adverse Event Reporting Description | No adverse events were reported. | |
| Arm/Group Title | Minocycline | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Minocycline | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Minocycline | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Minocycline | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/13 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Principal Investigator |
|---|---|
| Organization | Huntington Medical Research Institutes |
| Phone | 6263975840 |
| mrs@hmri.org |
- LKW-AB34