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

NCT01374438 | Completed Phase 2 Results

• 1 other identifier: MSDC-0160-C006
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; cognitive function; brain glucose utilization; FDG-PET

Outcome Measures

Primary Outcomes (1)

• Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum

  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 Outcomes (4)

• Change From Baseline in Global Cognitive Function Tests

  Days 1 (baseline) and 91

• Change From Baseline in Cognitive Function as Determined by the ADAS-Cog Subscale

  Days 1 (baseline) and 91

• Change From Baseline in Cognitive Function as Estimate With the Executive Function Scale

  Days 1 (baseline) and 91

• Change From Baseline in HMW Adiponectin of MSDC-0160 or Placebo Over 12 Weeks

  Days 1(baseline) and 91

Study Arms (2)

MSDC-0160 capsules

EXPERIMENTAL

MSDC tablets contained in #00 capsules

Drug: MSDC-0160

Placebo capsules

PLACEBO COMPARATOR

Placebo tablets contained in #00 capsules

Drug: Placebo

Interventions

MSDC-0160 DRUG

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

Also known as: Mitoglitazone

MSDC-0160 capsules

Placebo DRUG

Placebo capsules given once daily for 90 days

Placebo capsules

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Metabolic Solutions Development Company: lead

Study Sites (1)

Rush Memorial University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• 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.

  PMID: 24931567 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Interventions

MSDC-0160

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Jerry Colca
• Organization: Metabolic Solutions Development Company

jcolca@msdrx.com

269.343.8732

Study Officials

• Jerry R Colca, PhD

  MSDC

  STUDY DIRECTOR

• Raj C. Shah, MD

  Rush Memorial University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 16, 2011
• Study Start: July 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 18, 2014
• Results First Posted: November 5, 2014

Record last verified: 2014-11

Locations

US (1)