Alzheimer's DiseasePhase 2NCT01374438
3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease
A Phase 2 study testing MSDC-0160 in people with Alzheimer's Disease, run by Metabolic Solutions Development Company at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- MSDC-0160
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rush Memorial University Medical Center
Chicago, Illinois, 60612
About this study
Official title: 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.
Read the 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.
- Conditions
- Alzheimer's Disease
- Being tested
- MSDC-0160, Placebo
- Keywords
- Alzheimer's disease, cognitive function, brain glucose utilization, FDG-PET
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSDC-0160Drug
Also called Mitoglitazone
MSDC-0160 150 mg capsules given once daily for 90 days
PlaceboDrug
Placebo capsules given once daily for 90 days
| Study group | Role | What they receive |
|---|---|---|
| MSDC-0160 capsules | Experimental | MSDC tablets contained in #00 capsules Receives: Drug: MSDC-0160 |
| Placebo capsules | Placebo comparator | Placebo tablets contained in #00 capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Days 1(baseline) and 91
Secondary outcomes (4)
Change From Baseline in Global Cognitive Function Tests
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.
Measured: Days 1 (baseline) and 91
Change From Baseline in Cognitive Function as Determined by the ADAS-Cog Subscale
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).
Measured: Days 1 (baseline) and 91
Change From Baseline in Cognitive Function as Estimate With the Executive Function Scale
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.
Measured: Days 1 (baseline) and 91
Change From Baseline in HMW Adiponectin of MSDC-0160 or Placebo Over 12 Weeks
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.
Measured: Days 1(baseline) and 91
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2011 (estimated)
- Study startJul 2011
- Primary completionMar 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Metabolic Solutions Development Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jerry R Colca, PhD, Study director, MSDCRaj C. Shah, MD, Principal investigator, Rush Memorial University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01374438
- Sponsor's protocol ID
- MSDC-0160-C006
- Status last verified
- Nov 2014
- First submitted
- 14 Jun 2011
- Last updated
- 18 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24931567
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01374438
- Acronym / sponsor ID
- MSDC-0160-C006
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, cognitive function, brain glucose utilization, FDG-PET
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Metabolic Solutions Development CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 Jun 2011 (estimated)
- Results
- Posted 5 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSDC-0160 capsules | Experimental | Drug: MSDC-0160MSDC tablets contained in #00 capsules |
| Placebo capsules | Placebo comparator | Drug: PlaceboPlacebo tablets contained in #00 capsules |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSDC-0160Also: MitoglitazoneMSDC-0160 150 mg capsules given once daily for 90 days | Drug | MSDC-0160 capsules |
| PlaceboPlacebo capsules given once daily for 90 days | Drug | Placebo capsules |
Primary outcome
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.
4 secondary outcomes
Change From Baseline in Global Cognitive Function Tests
Time frame: 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
Change From Baseline in Cognitive Function as Estimate With the Executive Function Scale
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24931567Shah 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry R Colca, PhD study director
MSDC
Raj C. Shah, MD principal investigator
Rush Memorial University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MSDC-0160 in people with Alzheimer's Disease, run by Metabolic Solutions Development Company at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01374438, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2014.