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
| City: |
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Chicago |
| State: |
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Illinois |
| Zip Code: |
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60612 |
| Conditions: |
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Alzheimer's Disease |
| Purpose: |
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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.
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| Study Summary: |
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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:
1. 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.
2. Estimate the effect size of MSDC-0160 versus placebo on 3-month change in brain glucose
utilization, using FDG-PET voxel-based analysis.
3. 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.
4. Estimate the effect size of MSDC-0160 versus placebo on 3-month change in cognitive
function as determined by the ADAS-Cog subscale.
5. Estimate the effect of 3-months of MSDC-0160 treatment versus placebo on a 9-item
executive function scale.
6. 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.
7. Explore whether changes in peripheral inflammatory biomarkers correlate with changes in
3-month brain glucose utilization in MSDC-0160 users.
8. Investigate the safety of MSDC-0160 versus placebo using reports of early study
termination and adverse events.
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| Criteria: |
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Inclusion Criteria:
1. Male or females 55-85 years of age.
2. Females should be either postmenopausal or surgically sterilized. Males with female
partners of child-bearing potential must use contraception if engaging in sexual
intercourse.
3. Diagnosis of probable Alzheimer's disease based on NIA-AA criteria with MMSE scores
of 20 or greater.
4. 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.
5. 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:
1. Diagnosis of diabetes, including use of anti-diabetic medications, or fasting plasma
glucose >125 mg/dl or Hemoglobin A1c>6.4%.
2. 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).
3. 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.
4. History of heart failure (including CHF).
5. Previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within
the past 6 months prior to screening.
6. 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.
7. 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.
8. Current or history of severe or unstable disorder (medical or psychiatric) requiring
treatment that may make the subject unlikely to complete the study.
9. Malignancy (other than non-melanoma skin cancer) within the last 5 years.
10. Known history of HIV, hepatitis B, or hepatitis C.
11. 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.
12. 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.
13. Known or suspected intolerance or hypersensitivity to the study drugs, closely
related compounds, or any of their stated ingredients.
14. History of alcohol or drug abuse within 6 months of screening.
15. 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.
16. 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.
17. 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.
18. 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.
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| NCT ID: |
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NCT01374438 |
| Primary Contact: |
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Study Director
Jerry R Colca, PhD
MSDC
Lindsay Franti
Phone: (312) 563-4111
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| Backup Contact: |
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N/A |
| Location Contact: |
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Chicago, Illinois 60612
United States
There is no listed contact information for this specific location.
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 19, 2013 |
| Modifications to this listing: |
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