Alzheimers Disease MedDRA version: 8.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Name: Rosiglitazone XR
Product Code: BRL-049653/461
Pharmaceutical Form: Tablet
INN or Proposed INN: Rosiglitazone Maleate (RSG)
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Is male, or if female meets one or more of the following criteria: • Post-menopausal females defined as menopause is defined as >6 months without menstrual period with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges). Women who are on HRT treatment, and have not been confirmed as post-menopausal should be advised to use contraception (See Appendix 4) • Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 2. Meets the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer's disease, regardless of date of diagnosis relative to study entry date (See Appendix 5). 3. Has an Alzheimer's disease status of mild to moderate, as classified by a Mini Mental State Examination (MMSE) score of 16 – 26 inclusive at screening. 4. Is aged ? 50 to ? 85 years. 5. Prior and current use of medication corresponds with the criteria listed in Appendix 3. 6. Has the ability to comply with requirements of cognitive and other testing. 7. Has a permanent caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status. (Subjects living alone or in a nursing home are not eligible). 8. Has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, provision of informed consent by cognitively intact legally acceptable representative . 9. Caregiver has provided full written informed consent prior to the performance of any protocol-specified procedure. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Is unsuitable for MRI scanning as assessed by local pre-MRI questionnaire . 2. Has a history of or suffers from claustrophobia. 3. Is unable to lie comfortably on a bed inside a PET camera with their head in the field of view for at least 60 minutes as assesed by physical examination and medical history (e.g. back pain, arthritis). 4. Has a history or presence of other neurological or other medical conditions that may influence the outcome or analysis of the PET scan results. Examples of such conditions include, but are not limited to stroke, traumatic brain injury, epilepsy or space occupying lesions. 5. History of Type I or Type II diabetes mellitus. 6. Fasting plasma glucose level >126 mg/dL (>7.0 mmol/L) or HbA1c >6.2% 7. History or clinical/laboratory evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV) (See Appendix 6). 8. Ejection fraction 100 bpm 2. Any previously unrecognised sustained or paroxysmal arrhythmia requiring further intervention e.g. anticoagulation, cardioversion, anti-arrhythmic agent, further investigation etc. 3. PR interval >0.3 s, 2nd or 3rd degree heart block, symptomatic bifascicular block, trifascicular block 4. Multifocal ventricular ectopy 5. Ventricular bigemini or couplets, triplets etc. 1. AF with a heart rate <=90 in subjects receiving appropriate anti-platelet or anticoagulant therapy 2. 1st degree heart block (PR<=0.3 s) 3. Subjects with a paced rhythm (further information required if subject has an Implantable Cardiac Defibrillator) 4. Atrial ectopic beats 5. Unifocal ventricular ectopic beats 6. Left or right bundle branch block 7. Asymptomatic bifascicular block 8. Left ventricular hypertrophy 9. Q waves present suggesting previous MI 10. Repolarisation abnormalities 9. History of new cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina) or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled. 10. History or clinical laboratory evidence of cerebrovascular disease (stroke, transient ischaemic attack, haemorrhage), or diagnosis of possible, probable or definite vascular dementia in accordance with National Institut
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare changes in cerebral glucose metabolism in subjects receiving a 12- month course of Rosiglitazone XR to those receiving placebo, including the time course of any changes. ;Primary end point(s): Change in global and regional cerebral glucose metabolism/Cerebral Metabolic Rate for glucose (CMRglu) between baseline and 12 months as measured by [18F]FDG uptake.; Secondary Objective: • To compare structural changes in the brains of subjects receiving a 12-month course of Rosiglitazone XR to those receiving placebo, as assessed by changes in volumetric MRI from baseline. • To compare changes in cognitive performance in subjects receiving a 12-month course of Rosiglitazone XR to those receiving placebo, including the time course of any changes. • To relate changes in cerebral glucose metabolism, cognitive performance and brain structure. • To compare changes in peripheral glucose metabolism and insulin sensitivity in subjects receiving a 12-month course of Rosiglitazone XR to those receiving placebo, including the time course of any changes. • To compare changes in lipid levels in subjects receiving a 12-month course of Rosiglitazone XR to those receiving placebo, including the time course of any changes. *See protocol for further secondary objectives | — |
Countries
United Kingdom
Outcome results
None listed