Minocycline in Patients With Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Brian D. Ross, MD, Huntington Medical Research Institutes
ClinicalTrials.gov Identifier:
NCT01463384
First received: October 25, 2011
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Mild Cognitive Impairment
Alzheimer's Disease
Drug: Minocycline
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MRI and MRS Diagnosis and Treatment Monitoring of Alzheimer's Disease With Novel Therapy

Resource links provided by NLM:


Further study details as provided by Huntington Medical Research Institutes:

Primary Outcome Measures:
  • Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) ] [ Designated as safety issue: No ]

    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). [ Time Frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) ] [ Designated as safety issue: No ]

    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) [ Time Frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged) ] [ Designated as safety issue: No ]

    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.



Enrollment: 13
Study Start Date: September 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Minocycline
Subjects will be administered 50mg minocycline twice daily.
Drug: Minocycline
50mg, twice daily for 6 months.
Other Name: Tetracycline

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.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01463384

Locations
United States, California
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
  More Information

Additional Information:
No publications provided

Responsible Party: Brian D. Ross, MD, Director, MR Unit, Huntington Medical Research Institutes
ClinicalTrials.gov Identifier: NCT01463384     History of Changes
Other Study ID Numbers: LKW-AB34
Study First Received: October 25, 2011
Results First Received: October 25, 2012
Last Updated: September 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Huntington Medical Research Institutes:
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Neuroinflammation
Mild Cognitive Impairment
Alzheimer's Disease
Minocycline

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014