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

NCT00265148 | Completed Phase 2 Results

• 2 other identifiers: BRL-49653/4612005-005089-34
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12

  Global CMRGlu index was related to grey matter of brain. Regional CMRGlu index was related to assessment of different regions of brain namely posterior cingulate gyrus, frontal lobe, parietal lobe, posterior temporal lobe, cerebellum, and medial temporal lobe. Evaluation of medial temporal lobe CMRGlu included assessment of medial anterior temporal lobe, paraHippocampal Ambiens gyrus, amygdala, and hippocampus. The regional CMRGlu index is directly proportional to the true metabolic rate of glucose. Baseline was defined as Day 1 of the 12 months treatment period. Change from Baseline is the value at indicated time point minus the Baseline value. Data has been presented for arithmetic mean; however, statistical analysis has been presented for adjusted or least square (LS) mean.

  Baseline (Day 1) and Month 12

Secondary Outcomes (26)

• Change From Baseline (Day 1) in CMRGlu Indices at Months 1 and 6

  Baseline (Day 1), Months 1, and 6

• Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test

  Baseline (Day 1), and Months 1, 6, and 12

• Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12

  Baseline (Day 1), Months1, 6, and 12

• Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period

  Baseline (Day 1), Months 1, 6, and 12

• Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period

  Baseline (Day 1) and up to 12 months

Study Arms (2)

Rosiglitazone

EXPERIMENTAL

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

Drug: Rosiglitazone

Placebo

OTHER

Placebo dummy to match

Other: Placebo

Interventions

Rosiglitazone DRUG

Extended Release Tablets

Rosiglitazone

Placebo OTHER

Placebo dummy to match

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Litchfield Park, Arizona, 85340, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85259, United States

Location

GSK Investigational Site

Sun City, Arizona, 85351, United States

Location

GSK Investigational Site

Tucson, Arizona, 85724, United States

Location

GSK Investigational Site

Los Angeles, California, 90024, United States

Location

GSK Investigational Site

Belmont, Massachusetts, 02478, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

GSK Investigational Site

Montreal, Quebec, H3T 1E2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4H 1R3, Canada

Location

GSK Investigational Site

Liverpool, L9 7LJ, United Kingdom

Location

GSK Investigational Site

Manchester, M20 3LJ, United Kingdom

Location

GSK Investigational Site

Swindon, SN1 4HZ, United Kingdom

Location

GSK Investigational Site

West End, Southampton, SO30 3JB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 20930300 DERIVED

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2005
• First Posted: December 14, 2005
• Study Start: May 18, 2004
• Primary Completion: July 10, 2008
• Study Completion: July 10, 2008
• Last Updated: November 18, 2020
• Results First Posted: November 18, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (4); US (9); CA (2)