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

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ClinicalTrials.gov Identifier: NCT00265148
Recruitment Status : Completed
First Posted : December 14, 2005
Last Update Posted : November 16, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE December 12, 2005
First Posted Date  ICMJE December 14, 2005
Last Update Posted Date November 16, 2016
Study Start Date  ICMJE May 2004
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2005)
Change from baseline in global and regional functional brain activity at 12 months
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00265148 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2010)
  • Change in functional brain activity at other timepoints; changes in cognition and clinical scales of AD status; changes in brain structure; safety and tolerability; changes in blood biomarkers and insulin sensitivity; genetic (apolipoprotein E) status
  • Changes in global and regional CMRglu between baseline and other scan time points as measured by [18F]FDG uptake.
  • Changes in cognitive tests and clinical scales of AD status from baseline.
  • Global changes in brain structure from baseline as measured by structural MRI from baseline.
  • Changes in blood borne biomarkers from baseline: Markers of glucose metabolism (fasting plasma glucose; fasting plasma insulin: HbA1C); Lipid levels; Inflammatory markers; Immunology markers; Putative markers of disease burden.
  • Changes in insulin sensitivity from baseline: Homeostasis Model Assessment; Body Mass Index
  • Polymorphism status with respect to genetic markers: Apolipoprotein-E
  • Measures of safety and tolerability: Vital signs, 12-Lead ECGs, Haematology and clinical chemistry evaluations, Adverse events, Measures of fluid retention: body weight; haematocrit; clinical examination
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2005)
Change in functional brain activity at other timepoints; changes in cognition and clinical scales of AD status; changes in brain structure; safety and tolerability; changes in blood biomarkers and insulin sensitivity; genetic (apolipoprotein E) status
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brain Imaging Study Of Rosiglitazone Efficacy And Safety In Alzheimer's Disease
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) on Cerebral Glucose Utilization and Cognition in Subjects With Mild to Moderate Alzheimer's Disease (AD)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Rosiglitazone
    Extended Release Tablets
  • Other: Placebo
    Placebo dummy to match
Study Arms  ICMJE
  • Experimental: Rosiglitazone
    4 mg once a day for 1 month increasing to 8 mg once a day (Extended Released Tablets)
    Intervention: Drug: Rosiglitazone
  • Placebo
    Placebo dummy to match
    Intervention: Other: Placebo
Publications * 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 [¹⁸F]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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 13, 2005)
80
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2008
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00265148
Other Study ID Numbers  ICMJE BRL-49653/461
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP