Minocycline in Patients With Alzheimer's Disease

NCT01463384 | Completed Phase 2 Results

• 1 other identifier: LKW-AB34
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Keywords

Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neuroinflammation; Mild Cognitive Impairment; Alzheimer's Disease; Minocycline

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)

Study Arms (1)

Minocycline

ACTIVE COMPARATOR

Subjects will be administered 50mg minocycline twice daily.

Drug: Minocycline

Interventions

Minocycline DRUG

50mg, twice daily for 6 months.

Also known as: Tetracycline

Minocycline

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Huntington Medical Research Institutes: lead

Study Sites (1)

Huntington Medical Research Institutes

Pasadena, California, 91105, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Neuroinflammatory Diseases; cyclopia sequence

Interventions

Minocycline; Tetracycline

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Principal Investigator
• Organization: Huntington Medical Research Institutes

mrs@hmri.org

6263975840

Study Officials

• Brian D Ross

  Huntington Medical Research Institutes

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, MR Unit

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: November 1, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: September 25, 2014
• Results First Posted: September 25, 2014

Record last verified: 2014-09

Locations

US (1)