- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01374438
3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease
November 5, 2014 updated by: Metabolic Solutions Development Company
A 3-month Randomized, Double-Blind, Placebo-Controlled, Feasibility Study to Evaluate the Effects of MSDC-0160 on Brain Glucose Utilization, Cognition, Safety and Tolerability in Older Persons With Mild Alzheimer's Disease
This study will evaluate the effect of 150 mg MSDC-0160 taken daily for 90 days compared to the effect of placebo on changes in brain glucose utilization using FDG-PET and cognition in older persons with mild Alzheimer's disease.
Safety and tolerability of MSDC-0160 in this population will also be studied.
These results will be used to design larger studies of MSDC-0160 in persons with mild Alzheimer's disease.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The specific objective is to examine the feasibility of conducting future large scale studies on the efficacy of MSDC-0160 in persons with mild Alzheimer's disease. Efficacy and safety will be assessed as follows:
- Estimate the effect size of 150 mg daily MSDC-0160 versus placebo on 3-month change in brain glucose utilization using FDG-PET pre-specified regions of interest analysis. The a priori regions of interest (ROI) will include five bilateral regions: posterior cingulate, parietal cortex (angular gyrus), lateral temporal cortex, medial temporal cortex, and anterior cingulate-medial frontal cortex.
- Estimate the effect size of MSDC-0160 versus placebo on 3-month change in brain glucose utilization, using FDG-PET voxel-based analysis.
- Estimate the effect size of MSDC-0160 treatment versus placebo on 3-month change in cognitive function as determined by global cognitive function on a neuropsychological battery of 19 tests.
- Estimate the effect size of MSDC-0160 versus placebo on 3-month change in cognitive function as determined by the ADAS-Cog subscale.
- Estimate the effect of 3-months of MSDC-0160 treatment versus placebo on a 9-item executive function scale.
- Explore whether baseline levels of peripheral inflammatory biomarkers (HMW adiponectin, TNFα, IL-6, hsCRP, and FFA) or genotypes including, but not limited to, the apolipoprotein ε4 allele explain the heterogeneity in baseline level of brain glucose utilization and, in MSDC-0160 users, 3-month brain glucose utilization.
- Explore whether changes in peripheral inflammatory biomarkers correlate with changes in 3-month brain glucose utilization in MSDC-0160 users.
- Investigate the safety of MSDC-0160 versus placebo using reports of early study termination and adverse events.
Study Type
Interventional
Enrollment (Actual)
29
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
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Illinois
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Chicago, Illinois, United States, 60612
- Rush Memorial University Medical Center
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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 85 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or females 55-85 years of age.
- Females should be either postmenopausal or surgically sterilized. Males with female partners of child-bearing potential must use contraception if engaging in sexual intercourse.
- Diagnosis of probable Alzheimer's disease based on NIA-AA criteria with MMSE scores of 20 or greater.
- Willing and able to take part in up to six study visits over a 5-month period, with the support of a caregiver as needed.
- Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study, with the support of a caregiver as needed.
Exclusion Criteria:
- Diagnosis of diabetes, including use of anti-diabetic medications, or fasting plasma glucose >125 mg/dl or Hemoglobin A1c>6.4%.
Unable to participate in FDG-PET scanning, including:
- Inability to cooperate/claustrophobia (no sedation offered for this protocol).
- Inability to lie still on the scanner bed for 40 minutes.
- Total radiation dose exposure to the subject in any given year exceeds the limits of annual and total dose commitment of 50 mSv (5 REMs). The two FDG-PET scans will result in an approximate exposure of 10 mSv (1 REM).
- Diagnosis of significant neurological/psychiatric disease other than AD, including, but not limited to, any of the following: vascular dementia according to NINDS-AIREN criteria, space occupying cerebral lesion, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, and seizures.
- History of heart failure (including CHF).
- Previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to screening.
- Inability to undergo a clinical (1.5T) MRI of the brain without contrast and lack of a usable (less the 12 months prior to screening) MRI on record. Contraindications to undergoing an MRI of the brain include, but are not limited to, pacemakers; implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; and, other magnetic, electronic or mechanical implants or clinical findings that in the judgment of the investigator would pose a potential hazard in combination with MRI.
- ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that exceed 2 mg/dL; serum creatinine >1.5 mg/dL in men or > 1.4 mg/dL in women.
- Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the subject unlikely to complete the study.
- Malignancy (other than non-melanoma skin cancer) within the last 5 years.
- Known history of HIV, hepatitis B, or hepatitis C.
- Blood pressure greater than 160/100 mmHg. Subjects with elevated BP will be allowed at the discretion of the principal investigator. Individuals with hypertension must have been stabilized to the current treatment regimen for at least 6 weeks prior to screening and not need adjustments to their treatment regimen during the entire study period.
- Change in other medications to treat Alzheimer's disease within 3 months prior to screening. Change in medication to treat other conditions within 6 weeks prior to screening or during the study period.
- Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds, or any of their stated ingredients.
- History of alcohol or drug abuse within 6 months of screening.
- Have participated in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
- Single 12-lead ECG demonstrating a QTcB >450 msec or other clinically significant finding at screening. A single repeat ECG may be done at the investigator's discretion.
- Any surgical or medical condition which may significantly alter the absorption of any drug substance including, but not limited to, any of the following: history of major gastrointestinal tract surgery, currently active inflammatory bowel syndrome.
- Evidence of clinically relevant pathology that in the investigator's opinion could interfere with the study results or put the subject's safety at risk.
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: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: MSDC-0160 capsules
MSDC tablets contained in #00 capsules
|
MSDC-0160 150 mg capsules given once daily for 90 days
Other Names:
|
PLACEBO_COMPARATOR: Placebo capsules
Placebo tablets contained in #00 capsules
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Placebo capsules given once daily for 90 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum
Time Frame: Days 1(baseline) and 91
|
Investigate the effect of 150 mg daily MSDC-0160 vs placebo on 3-month change in brain glucose utilization using FDG-PET pre-specified regions of interest analysis referenced to cerebellum, including five bilateral regions: posterior cingulate, parietal cortex (angular gyrus), lateral temporal cortex, medial temporal cortex, and anterior cingulate-medial frontal cortex.
Results are reported as Standardized Uptake Value Ratios.
A change from baseline in the metabolic rate of glucose that is ≥0 indicates maintenance of brain glucose utilization, whereas values <0 indicate a decline in brain glucose utilization.
|
Days 1(baseline) and 91
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Global Cognitive Function Tests
Time Frame: Days 1 (baseline) and 91
|
Change from baseline in cognitive function, as determined by global cognitive function on a neuropsychological battery of 19 tests, following 3 months treatment with MSDC-0160 versus placebo.
A summary measure of global cognitive function was constructed by converting raw scores from 19 individual tests into z-scores as described by Bennett DA, et al., The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort, Neuroepidemiology.
2005;25(4):163-175.
|
Days 1 (baseline) and 91
|
Change From Baseline in Cognitive Function as Determined by the ADAS-Cog Subscale
Time Frame: Days 1 (baseline) and 91
|
Alzheimer's Disease Assessment Scale - Cognitive Subscale, an assessment of cognitive ability.
Scores on 11 individual tasks were summed to produce the reported total score, with a possible range of 0 (no impairment) to 70 (severe impairment).
|
Days 1 (baseline) and 91
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Change From Baseline in Cognitive Function as Estimate With the Executive Function Scale
Time Frame: Days 1 (baseline) and 91
|
Estimate of the effect of 3-months of MSDC-0160 treatment versus placebo on a 9-item executive function scale.
A summary measure of executive function was constructed by converting raw scores from 9 individual tests into z-scores as described by Bennett DA, et al., The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort, Neuroepidemiology.
2005;25(4):163-175.
|
Days 1 (baseline) and 91
|
Change From Baseline in HMW Adiponectin of MSDC-0160 or Placebo Over 12 Weeks
Time Frame: Days 1(baseline) and 91
|
Estimate the effect of 150 mg daily MSDC-0160 versus placebo on levels of high molecular weight adiponectin.
Increases in HMW adiponectin suggest improved insulin sensitivity.
|
Days 1(baseline) and 91
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Jerry R Colca, PhD, MSDC
- Principal Investigator: Raj C. Shah, MD, Rush Memorial University Medical Center
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.
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
July 1, 2011
Primary Completion (ACTUAL)
March 1, 2013
Study Completion (ACTUAL)
May 1, 2013
Study Registration Dates
First Submitted
June 14, 2011
First Submitted That Met QC Criteria
June 15, 2011
First Posted (ESTIMATE)
June 16, 2011
Study Record Updates
Last Update Posted (ESTIMATE)
November 18, 2014
Last Update Submitted That Met QC Criteria
November 5, 2014
Last Verified
November 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MSDC-0160-C006
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.
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