Brain Imaging Study Of Rosiglitazone Efficacy And Safety In Alzheimer's Disease

NCT ID: NCT00265148

Last Updated: 2020-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-18
• Study Completion Date: 2008-07-10

Brief Summary

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).

Conditions

Alzheimer's Disease

Keywords

rosiglitazone; cognition; cerebral glucose metabolism; positron emission tomography (PET); Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Rosiglitazone

4 mg once a day for 1 month increasing to 8 mg once a day (Extended Released Tablets)

Group Type: EXPERIMENTAL

Rosiglitazone

Intervention Type: DRUG

Extended Release Tablets

Placebo

Placebo dummy to match

Group Type: OTHER

Placebo

Intervention Type: OTHER

Placebo dummy to match

Interventions

Rosiglitazone

Extended Release Tablets

Intervention Type: DRUG

Placebo

Placebo dummy to match

Intervention Type: OTHER

Eligibility Criteria

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 </= 85 years Prior and current use of medication corresponds with criteria listed in Appendix 3.

• 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 fraction</=40% determined by echocardiogram, or any other abnormality on echocardiography which in the view of the investigator required further investigation or intervention, or significant abnormalities on screening ECG (in accordance with the definitions below). Significant ECG abnormalities for the purposes of this study. Detection of any of the following abnormalities renders the subject ineligible for the study: 1. ECG heart rate <50 and >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. 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 (</=200pg/mL), syphilis serology, thyroid stimulating hormone.
• 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Litchfield Park, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Scottsdale, Arizona, United States

GSK Investigational Site

Sun City, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Belmont, Massachusetts, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Liverpool, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Swindon, , United Kingdom

GSK Investigational Site

West End, Southampton, , United Kingdom

Countries

United States; Canada; United Kingdom

References

Tzimopoulou S, Cunningham VJ, Nichols TE, Searle G, Bird NP, Mistry P, Dixon IJ, Hallett WA, Whitcher B, Brown AP, Zvartau-Hind M, Lotay N, Lai RY, Castiglia M, Jeter B, Matthews JC, Chen K, Bandy D, Reiman EM, Gold M, Rabiner EA, Matthews PM. A multi-center randomized proof-of-concept clinical trial applying [(1)(8)F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's disease. J Alzheimers Dis. 2010;22(4):1241-56. doi: 10.3233/JAD-2010-100939.

Reference Type: DERIVED

PMID: 20930300 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Dataset Specification

View Document

Document Type: Study Protocol

View Document

Document Type: Clinical Study Report

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

2005-005089-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BRL-49653/461

Identifier Type: -

Identifier Source: org_study_id