| Participants |
Condition: T2DM and cognitive impairment
Enrollment: estimated 120 participants of interest to this review
Inclusion criteria: T2DM, mild to moderate cognitive impairment as defined by a MMSE score ≤ 26 at screening, Hachinski ischaemia score ≤ 4 at screening, brain CT or MRI scan and neurological exam performed at screening, showing no evidence of any focal neurological changes (i.e. hemiplegia, hemidysaesthesia, aphasia).
Exclusion criteria: history of significant psychiatric illness such as schizophrenia or bipolar affective disorder, major depressive disorder (according to DSM‐IV) in the past year, or current active depression requiring initiation of treatment, history or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, haemorrhage), structural abnormality, epilepsy, head injuries, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease, evidence of the following disorders: current vitamin B12 deficiency, malignancy, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), clinically significant anaemia (i.e. Hb < 11 g/dL for males or < 10 g/dL for females) which would prevent accurate assessment of HbA1c, current or recent drug or alcohol abuse or dependence (defined by DSM‐IV criteria for substance‐related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia, heart rate ≤ 50 beats/min or ≥ 110 beats/min, history of cardiovascular event within the last 4 months (i.e. acute coronary syndrome (myocardial infarction, unstable angina) or significant arrhythmia, intervention, percutaneous coronary intervention, or major intervention (e.g. cardiac surgery or angiography plus stenting), SBP ≥ 180 or < 90 mmHg at the time of screening, history or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class Ⅱ to IV cardiac status), abnormal kidney function tests (> 1.5 the upper limit of normal (UNL)), ALT, AST, or alkaline phosphatase values > 2.5 times the ULN, total bilirubin values > 1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or cirrhosis, Child‐Pugh Class B/C), asthma and chronic obstructive pulmonary disease, history or presence of gastro‐intestinal, or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, T2DM being treated with other than PPARγ agonist (e.g. rosiglitazone), or an insulin secretagogue (e.g. a sulphonylurea), a history of allergic reaction to pioglitazone and metformin, unable to comply with procedures for cognitive and other testing. |
