3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease

NCT ID: NCT01374438

Last Updated: 2014-11-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2013-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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MSDC-0160 capsules

MSDC tablets contained in #00 capsules

Group Type EXPERIMENTAL

MSDC-0160

Intervention Type DRUG

MSDC-0160 150 mg capsules given once daily for 90 days

Placebo capsules

Placebo tablets contained in #00 capsules

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules given once daily for 90 days

Interventions

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MSDC-0160

MSDC-0160 150 mg capsules given once daily for 90 days

Intervention Type DRUG

Placebo

Placebo capsules given once daily for 90 days

Intervention Type DRUG

Other Intervention Names

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Mitoglitazone

Eligibility 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.
Minimum Eligible Age

55 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Metabolic Solutions Development Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jerry R Colca, PhD

Role: STUDY_DIRECTOR

MSDC

Raj C. Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Rush Memorial University Medical Center

Locations

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Rush Memorial University Medical Center

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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Shah RC, Matthews DC, Andrews RD, Capuano AW, Fleischman DA, VanderLugt JT, Colca JR. An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease. Curr Alzheimer Res. 2014;11(6):564-73. doi: 10.2174/1567205011666140616113406.

Reference Type RESULT
PMID: 24931567 (View on PubMed)

Other Identifiers

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MSDC-0160-C006

Identifier Type: -

Identifier Source: org_study_id