This is a placebo-controlled study evaluating the effects of rosiglitazone on functional
brain activity and cognition in patients with mild to moderate Alzheimer's Disease (AD).
Inclusion criteria:
- Is male, or if female meets one or more of the following criteria:
- Post-menopausal females defined as menopause is defined as>6months 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.
- 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) 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.
Is aged >/= 50 to - Has the ability to comply with requirements of cognitive and other testing.
- 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).
- 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 (Where this is in accordance with local laws, regulations
and ethics committee policy.) Caregiver has provided full written informed consent
prior to the performance of any protocol-specified procedure.
Exclusion criteria:
- Is unsuitable for MRI scanning as assessed by local pre-MRI questionnaire (GSK to
review.)
- Has a history of or suffers from claustrophobia.
- 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 assessed by physical examination and medical
history (e. g. back pain, arthritis).
- 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.
- History of Type I or Type II diabetes mellitus.
- Fasting plasma glucose level>126mg/dL (>7. 0mmol/L) or HbA1c>6. 2%.
- History or clinical/laboratory evidence of moderate congestive heart failure defined
by the New York Heart Association criteria (class I-IV)(See Appendix 6).
Ejection fraction100 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. ECG abnormalities
permitted at entry to this study. A subject will not be rendered ineligible by the presence
of any of the following abnormalities: 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. Asymptomatice bifascicular block.
8. Left ventricular hypertrophy. 9. Q waves present suggesting previous MI. 10.
Repolarisation abnormalities 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.
- 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 Institute of Neurological Disorders and
Stroke, and Association Internationale pour la Recherche et l'Enseignement en
Neurosciences (NINDS-AIREN) criteria (See Appendix 8).
- History or evidence of any other CNS disorder that could be interpreted as a cause of
dementia: e. g. structural abnormality, epilepsy, infectious or
inflammatory/demyelinating CNS conditions, Parkinson's disease.
Significant peripheral oedema at the time of screening as assessed by Clinical Evaluation
of Oedema and/or Signs of Congestive Heart Failure (Appendix 14)
- History of major psychiatric illness such as schizophrenia or bipolar affective
disorder, or current depression (score on Hospital Anxiety and Depression Scale (HADS)
depression questions >7, See Appendix 9).
Systolic blood pressure >165 mmHg or diastolic blood pressure >95 mmHG whilst receiving
optimal antihypertensive therapy according to local practice.
Clinically significant anaemia (i. e.haemoglobin <11g/dL for males or <10 g/dL for females)
or presence of haemoglobinopathies which would prevent accurate assessment of HbA1c.
Renal dysfunction, defined as creatinine clearance <30 ml/min (calculated from serum
creatinine using the Cockcroft-Gault formula, See Appendix 10).
ALT, AST, total bilirubin, or alkaline phosphatase >2. 5 times the upper limit of normal
laboratory range, or history of severe hepatobiliary disease (e. g. hepatitis B or C, or
cirrhosis (Childs-Pugh classes B/C)) without enzyme elevation.
- Fasting triglycerides >12mmol/L Abnormal/positive result within the past 12 months or
at screening for any of the following tests: vitamin B12 ( - History or presence of gastro-intestinal, hepatic or renal disease or other condition
known to interfere with absorption, distribution, metabolism or excretion of drugs.
any clinically relevant abnormality, medical or psychiatric condition, which, in the
opinion of the investigator, makes the subject unsuitable for inclusion in the study.
- Has donated >/= ml of blood within the past 2 months. Use of any other investigational
agent within 30 days or 5 half-lives (whichever is longer) prior to the screening
visit.
History of alcohol abuse, or of drug abuse within the past 6 months (or has tested positive
for drugs of abuse at screening).
Subject is unable (with assistance, if appropriate) to take study medication as prescribed
throughout the study.
- History of non-compliance with prescribed medication, or risk of non-compliance with
study medication or procedures.
Subject is an immediate family member or employee of the participating investigator or of
any of the participating site staff.
Shows any neurological abnormality by MRI, which in the opinion of the Principal
Investigator would introduce additional risk factors, study procedures or effect endpoint
data. MRI scanning will only be conducted on subjects who satisfy all other eligibility
criteria.
- History of bone marrow transplant Exhibits screening/baseline results not consistent
with AD e. g. radiological findings, or results on cognitive tests.
Use of tacrine within 30 days prior to the screening visit.
GSK Clinical Trials Call Center, Sun City, Arizona 85351, United States
GSK Clinical Trials Call Center, Scottsdale, Arizona 85259, United States
GSK Clinical Trials Call Center, Phoenix, Arizona 85006, United States
GSK Clinical Trials Call Center, Belmont, Massachusetts 02478, United States
GSK Clinical Trials Call Center, Ann Arbor, Michigan 48109, United States
GSK Clinical Trials Call Center, Durham, North Carolina 27705, United States
GSK Clinical Trials Call Center, Montreal, Quebec H3T 1E2, Canada
GSK Clinical Trials Call Center, Montreal, Quebec H4H 1R3, Canada
