Insulin Resistance and Mild Cognitive Impairment (IRMCI) Study

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Dementia (Alzheimer's Disease) is sometimes called "Type 3 Diabetes" because of the strong connection between Type 2 diabetes (a function of insulin resistance) with Dementia.

The investigators therefore hypothesize that Reducing Insulin Resistance using Intensive Lifestyle Intervention (Exercise and Weight loss) + Metformin Treatment in Prediabetic & diet-control-only Diabetic overweight and mildly cognitively impaired individuals 55 years or older would lead to better Cognitive Function (compared to standard care) after 2 years.

Subjects will be monitored and assessed using a battery of Cognitive and psychological tests and PET scans to demonstrate glucose utilization in the relevant areas of the brain.

This 3-year open-label study aims to recruit 360 subjects with 50% (180 subjects) randomized to receiving Intensive lifestyle intervention with Metformin (if diabetic) vs the other 50% who would receive only the usual standard level of care in the primary care setting.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SingHealth Polyclinics
• Collaborators: Agency for Science, Technology and Research; Changi General Hospital; Duke-NUS Graduate Medical School; Khoo Teck Puat Hospital; National University Hospital, Singapore; National University, Singapore; Singapore Clinical Research Institute; Singapore General Hospital
• Treatments: Insulin; Metformin

Criteria

Inclusion Criteria:

1. Chinese Singapore Citizen or Permanent Resident.

2. BMI of 23 or higher (Asian criteria for overweight and obese, Ministry of Health Recommendation, Singapore); and/or Waist Circumference: ≥ 90cm and ≥ 80cm for Chinese men and women respectively.

3. Prediabetes (if Not diabetic):

• Impaired fasting glucose (IFG): (ADA criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL), and/or

• Impaired glucose tolerance (IGT) (WHO and ADA criteria: two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test,. and/or

• HbA1C: 5.7- 6.4% (ADA criteria)

4. Type 2 Diabetes (if Not prediabetic) yet to be treated with anti-diabetic drug treatment ('on diet control only'), with HbA1c <8.0% OR Diabetics who have been taken off medication for =/> 1 year with HbA1c< 8.0% will be considered for recruitment.

• If HbA1c is 8.0- 8.4% at any follow-up visit, then try diet and lifestyle control and repeat at next visit (i.e. 3 months later). If 2 consecutive repeat HbA1c readings are still 8.0-8.4% or if subjects choose to start on or increase medication for diabetes, then take out of study and start medication.

• If HbA1c =/>8.5% at any time after Recruitment, take out of study and start medication.

5. Mild Cognitive Impairment:

• The individual is neither normal nor demented;

• There is evidence of cognitive deterioration, shown by either objectively measured decline over time or subjective report of decline by self or informant in conjunction with objective cognitive deficits; and

• Activities of daily life are preserved and complex instrumental functions are either intact or minimally impaired.

• This will be operationalized in the study as:

• A Subjective memory or cognitive complaint by the patient and/or by the caregiver

• Objective cognitive deficit documented by performance on a battery of multiple-domain neuropsychological tests (See below): a score that is 1.0 SD or more below age- and education-adjusted local norms

• aMCI: Deficit in delayed recall subtest of the Rey Auditory Verbal Learning Test (RAVLT) and Story Memory test

• mdMCI: Deficit in language, executive function, visuospatial/constructional ability, block design, and attention.

• Generally intact Activities of Daily Living as measured by Instrumental and Basic Activities of Daily Living (IADL and BADL).

• No dementia:

Exclusion Criteria:

1. Contraindications to Metformin treatment: Creatinine of > 150umol/L, history of decompensated liver disease, liver cirrhosis, or unexplained elevated hepatic transaminases (ALT or AST >3x Upper Limit of Normal; Upper Limits as accepted by SingHealth Polyclinics as 66 U/L for ALT and 42 U/L). This contraindication would not affect Subjects with a history of high baseline ALT and/or AST which have been evaluated by a Hepatologist to be due to Non-alcoholic Fatty Liver Disease without cirrhosis.,

2. Severe Neuro-Musculoskeletal and Sensory Disabilities

3. Severe Psychiatric disorders (eg; alcohol abuse, severe depression, schizophrenia, bipolar disorder)

4. Illnesses that seriously reduce life expectancy or ability to participate in the trial

5. Congestive heart failure (New York Heart Association cardiac status classes 2, 3 or 4), Myocardial infarction or Coronary artery Bypass surgery or percutaneous coronary intervention within the past 6 months, Cardiac Arrhythmias, Severe Hypertension.

6. Concurrent use or recent use (within 1 week or 5 half lives of the drug whichever is longer) of drugs with anticholinesterase, sedating or central nervous system (CNS) side effects: antispasmodics, antiemetics, antidiarrhoeals, antihistamines, hypnotics, antidepressants, antipsychotics, bronchodilators.

7. Concurrent use of drugs (for >4 consecutive weeks) or use of drugs within 12 weeks of screening) that are known to adversely affect glucose tolerance and its interpretation: .

8. History of Hypersensitivity to any of the Study Drug or to Drugs of similar chemical classes

9. Use of an Investigative Drug within 30 days or 5 half-lives of the drug whichever is longer

10. Potentially Unreliable and/or judged by the investigator to be Unsuitable for the study.