Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Minocycline in Patients With Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01463384
Recruitment Status : Completed
First Posted : November 1, 2011
Results First Posted : September 25, 2014
Last Update Posted : September 25, 2014
Sponsor:
Information provided by (Responsible Party):
Brian D. Ross, MD, Huntington Medical Research Institutes

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Mild Cognitive Impairment Alzheimer's Disease Drug: Minocycline 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MRI and MRS Diagnosis and Treatment Monitoring of Alzheimer's Disease With Novel Therapy
Study Start Date : September 2011
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Minocycline
Subjects will be administered 50mg minocycline twice daily.
 Drug: Minocycline
50mg, twice daily for 6 months.
Other Name: Tetracycline


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: 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.


  2. Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC). [ Time Frame: 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.


  3. Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC) [ Time Frame: 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01463384


Locations
Layout table for location information
United States, California
Huntington Medical Research Institutes
Pasadena, California, United States, 91105
Sponsors and Collaborators
Huntington Medical Research Institutes
Investigators
Layout table for investigator information
Principal Investigator: Brian D Ross Huntington Medical Research Institutes
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Brian D. Ross, MD, Director, MR Unit, Huntington Medical Research Institutes
ClinicalTrials.gov Identifier: NCT01463384    
Other Study ID Numbers: LKW-AB34
First Posted: November 1, 2011    Key Record Dates
Results First Posted: September 25, 2014
Last Update Posted: September 25, 2014
Last Verified: September 2014
Keywords provided by Brian D. Ross, MD, Huntington Medical Research Institutes:
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Neuroinflammation
 Mild Cognitive Impairment
Alzheimer's Disease
Minocycline
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
 Mental Disorders
Cognition Disorders
Minocycline
Tetracycline
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action