Minocycline in Patients With Alzheimer's Disease

September 23, 2014 updated by: Brian D. Ross, MD, Huntington Medical Research Institutes

MRI and MRS Diagnosis and Treatment Monitoring of Alzheimer's Disease With Novel Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Pasadena, California, United States, 91105
        • Huntington Medical Research Institutes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Minocycline
Subjects will be administered 50mg minocycline twice daily.
Drug: Minocycline
50mg, twice daily for 6 months.
Other Names:
  • Tetracycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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).
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.
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)
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.
Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huntington Medical Research Institutes

Investigators

  • Principal Investigator: Brian D Ross, Huntington Medical Research Institutes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (ACTUAL)

October 1, 2012

Study Completion (ACTUAL)

October 1, 2012

Study Registration Dates

First Submitted

October 25, 2011

First Submitted That Met QC Criteria

October 28, 2011

First Posted (ESTIMATE)

November 1, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

September 25, 2014

Last Update Submitted That Met QC Criteria

September 23, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LKW-AB34

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Mild Cognitive Impairment

Clinical Trials on Minocycline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cote d'Ivoire

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe