Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease
A 24-week, Double-blind, Double-dummy, Randomized, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets), Donepezil, and Placebo as Monotherapy on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease. (REFLECT-1)
1 other identifier
interventional
862
20 countries
138
Brief Summary
Rosiglitazone (RSG) has been tested and is approved as a treatment for type II diabetes mellitus, a disease that occurs when the body ineffectively uses glucose. RSG XR, the investigational drug, is an extended-release form of RSG. This study tests whether RSG XR safely provides benefit to people with mild to moderate Alzheimer's disease (AD). RSG XR is a new approach to AD therapy and this study tests whether one's genes alter the effectiveness of RSG XR. Glucose is used by cells to make energy that they need to live. Changes in the ability of cells to use of glucose can lead to diseases like diabetes. Glucose levels may be lower in the brains of AD patients, and their brain cells may also use glucose less well than in unaffected people. The proper function of brain cells may be critical to memory and thought. If brain cells use glucose poorly, this might impact AD. Drugs that help brain cells properly use glucose may help a person maintain normal memory and thinking. Data suggesting that RSG may help AD patients was first seen in a small study at the Univ. of Washington and then from a larger international GSK study. In the first study, those receiving RSG once daily for 6 months scored better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that benefited most from therapy with RSG XR had a specific genetic pattern. They lacked the gene that caused them to produce apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene from one parent. Subjects with one copy of the APOE e4 gene remained fairly stable while those with two copies of APOE e4 continued to worsen during the 6-month treatment. This study will directly test the effect of RSG XR on people who either have or lack the APOE e4 gene.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2007
138 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2007
CompletedFirst Posted
Study publicly available on registry
January 29, 2007
CompletedStudy Start
First participant enrolled
February 27, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
September 5, 2008
CompletedResults Posted
Study results publicly available
May 19, 2017
CompletedMay 19, 2017
April 1, 2017
1.5 years
January 25, 2007
February 16, 2017
April 13, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Apolipoprotein epsilon4 (APOE e4) Negative Cohort
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in APOE4 Negative Cohort
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Secondary Outcomes (21)
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W8, W16, W24
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W8, W16, W24
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Neuropsychiatric Inventory (NPI) Total Score at W8, W16, W24
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Disability Assessment for Dementia (DAD) Scale Total Score at W8, W16, W24
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Short Term Memory Assessment Total Score (ADAS-Cog Q1 Plus Q7) at W8, W16, W24
Baseline (W0) and up to W24
- +16 more secondary outcomes
Study Arms (2)
Rosiglitazone
EXPERIMENTALXR (extended release) oral tablets
Placebo
OTHERPlacebo (Double-Dummy to Match)
Interventions
Eligibility Criteria
You may qualify if:
- Clinical diagnosis of probable Alzheimer's Disease (AD).
- MMSE score 10 to 23
- Has not taken an approved AD therapy in last 30 days.
- No previous hypersensitivity/intolerance to AChEIs
- Have a regular caregiver.
You may not qualify if:
- Diagnosis of vascular dementia.
- Type I or secondary diabetes mellitus.
- Type II diabetes mellitus treated with insulin, sulfonylurea or glipizide.
- History or evidence of congestive heart failure, clinically significant peripheral edema or anemia.
- History of significant psychiatric illness, major depressive disorder or current depression needing initiation of treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (138)
GSK Investigational Site
Phoenix, Arizona, 85004, United States
GSK Investigational Site
Los Angeles, California, 90036, United States
GSK Investigational Site
Newport Beach, California, 92660, United States
GSK Investigational Site
Palo Alto, California, 94305, United States
GSK Investigational Site
Reseda, California, 91355, United States
GSK Investigational Site
San Diego, California, 92120, United States
GSK Investigational Site
San Francisco, California, 94109, United States
GSK Investigational Site
Denver, Colorado, 80218, United States
GSK Investigational Site
Fairfield, Connecticut, 06824, United States
GSK Investigational Site
Norwalk, Connecticut, 06851, United States
GSK Investigational Site
Deerfield Beach, Florida, 33064, United States
GSK Investigational Site
Delray Beach, Florida, 33445, United States
GSK Investigational Site
Destin, Florida, 32541, United States
GSK Investigational Site
Hialeah, Florida, 33016, United States
GSK Investigational Site
Melbourne, Florida, 32901, United States
GSK Investigational Site
Plantation, Florida, 33317, United States
GSK Investigational Site
Sunrise, Florida, 33351, United States
GSK Investigational Site
Tampa, Florida, 33647, United States
GSK Investigational Site
Atlanta, Georgia, 30033, United States
GSK Investigational Site
Saint Paul, Minnesota, 55101, United States
GSK Investigational Site
Las Vegas, Nevada, 89146, United States
GSK Investigational Site
Kenilworth, New Jersey, 07033, United States
GSK Investigational Site
Toms River, New Jersey, 08755, United States
GSK Investigational Site
Albany, New York, 12208, United States
GSK Investigational Site
Syracuse, New York, 13210, United States
GSK Investigational Site
Centerville, Ohio, 45459, United States
GSK Investigational Site
Cleveland, Ohio, 44120, United States
GSK Investigational Site
Cleveland, Ohio, 44195, United States
GSK Investigational Site
Toledo, Ohio, 43623, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73112, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73118, United States
GSK Investigational Site
Tulsa, Oklahoma, 74104, United States
GSK Investigational Site
Jenkintown, Pennsylvania, 19046, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19102, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19104, United States
GSK Investigational Site
Memphis, Tennessee, 35105, United States
GSK Investigational Site
Nashville, Tennessee, 37212, United States
GSK Investigational Site
DeSoto, Texas, 75115, United States
GSK Investigational Site
San Antonio, Texas, 78229-3900, United States
GSK Investigational Site
San Antonio, Texas, 78229, United States
GSK Investigational Site
Middleton, Wisconsin, 53562-2215, United States
GSK Investigational Site
Graz-Eggenberg, A-8020, Austria
GSK Investigational Site
Hall in Tirol, A-6060, Austria
GSK Investigational Site
Linz, 4020, Austria
GSK Investigational Site
Linz, A-4020, Austria
GSK Investigational Site
Vienna, 1030, Austria
GSK Investigational Site
Vienna, A-1090, Austria
GSK Investigational Site
Vienna, A-1130, Austria
GSK Investigational Site
Plovdiv, 4000, Bulgaria
GSK Investigational Site
Sofia, 1113, Bulgaria
GSK Investigational Site
Sofia, 1431, Bulgaria
GSK Investigational Site
Sofia, 1527, Bulgaria
GSK Investigational Site
Viña del Mar, Región de Valparaíso, 252-0997, Chile
GSK Investigational Site
Providencia / Santiago, Región Metro de Santiago, 7500710, Chile
GSK Investigational Site
Puente Alto - Santiago, Región Metro de Santiago, 8207257, Chile
GSK Investigational Site
Santiago, Región Metro de Santiago, 7560356, Chile
GSK Investigational Site
Guangzhou, Guangdong, 510370, China
GSK Investigational Site
Beijing, 100083, China
GSK Investigational Site
Beijing, 100730, China
GSK Investigational Site
Shanghai, 200025, China
GSK Investigational Site
Shanghai, 200030, China
GSK Investigational Site
Shanghai, 200040, China
GSK Investigational Site
Tianjin, 300052, China
GSK Investigational Site
Dubrovnik, 20000, Croatia
GSK Investigational Site
Zagreb, 10000, Croatia
GSK Investigational Site
Tallinn, 10138, Estonia
GSK Investigational Site
Tallinn, 10614, Estonia
GSK Investigational Site
Tallinn, 10617, Estonia
GSK Investigational Site
Tartu, 51014, Estonia
GSK Investigational Site
Ellwangen, Baden-Wurttemberg, 73479, Germany
GSK Investigational Site
Tübingen, Baden-Wurttemberg, 72076, Germany
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89073, Germany
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89075, Germany
GSK Investigational Site
Günzburg, Bavaria, 89312, Germany
GSK Investigational Site
Munich, Bavaria, 80331, Germany
GSK Investigational Site
Munich, Bavaria, 81675, Germany
GSK Investigational Site
Nuremberg, Bavaria, 90402, Germany
GSK Investigational Site
Unterhaching, Bavaria, 82008, Germany
GSK Investigational Site
Hamburg, Hamburg, 20249, Germany
GSK Investigational Site
Hamburg, Hamburg, 22083, Germany
GSK Investigational Site
Hamburg, Hamburg, 22143, Germany
GSK Investigational Site
Bad Homburg, Hesse, 61348, Germany
GSK Investigational Site
Achim, Lower Saxony, 28832, Germany
GSK Investigational Site
Hanover, Lower Saxony, 30559, Germany
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, 19053, Germany
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, 19055, Germany
GSK Investigational Site
Baesweiler, North Rhine-Westphalia, 52499, Germany
GSK Investigational Site
Bielefeld, North Rhine-Westphalia, 33647, Germany
GSK Investigational Site
Bochum, North Rhine-Westphalia, 44892, Germany
GSK Investigational Site
Cologne, North Rhine-Westphalia, 50767, Germany
GSK Investigational Site
Duisburg, North Rhine-Westphalia, 47051, Germany
GSK Investigational Site
Jülich, North Rhine-Westphalia, 52428, Germany
GSK Investigational Site
Chemnitz, Saxony, 09111, Germany
GSK Investigational Site
Dresden, Saxony, 01097, Germany
GSK Investigational Site
Dresden, Saxony, 01307, Germany
GSK Investigational Site
Leipzig, Saxony, 04103, Germany
GSK Investigational Site
Halle, Saxony-Anhalt, 06122, Germany
GSK Investigational Site
Itzehoe, Schleswig-Holstein, 25524, Germany
GSK Investigational Site
Berlin, State of Berlin, 12163, Germany
GSK Investigational Site
Berlin, State of Berlin, 12167, Germany
GSK Investigational Site
Berlin, State of Berlin, 13125, Germany
GSK Investigational Site
Berlin, State of Berlin, 13507, Germany
GSK Investigational Site
Berlin, State of Berlin, 14163, Germany
GSK Investigational Site
Gera, Thuringia, 07551, Germany
GSK Investigational Site
Athens, 115 21, Greece
GSK Investigational Site
Melíssia, 151 27, Greece
GSK Investigational Site
Thessaloniki, 57010, Greece
GSK Investigational Site
Budapest, 1106, Hungary
GSK Investigational Site
Gyula, 5700, Hungary
GSK Investigational Site
Kaposvár, 7400, Hungary
GSK Investigational Site
Pécs, 7623, Hungary
GSK Investigational Site
Szeged, 6725, Hungary
GSK Investigational Site
Bangalore, 560034, India
GSK Investigational Site
Nagpur, 440010, India
GSK Investigational Site
Tirupati, 517507, India
GSK Investigational Site
Saltillo, Coahuila, 25000, Mexico
GSK Investigational Site
Monterrey, Nuevo León, 64660, Mexico
GSK Investigational Site
México, 14000, Mexico
GSK Investigational Site
Auckland, 0622, New Zealand
GSK Investigational Site
Karachi, 74800, Pakistan
GSK Investigational Site
Lahore, 54000, Pakistan
GSK Investigational Site
Lahore, 54590, Pakistan
GSK Investigational Site
Lima, Lima 13, Peru
GSK Investigational Site
Pasig, 1600, Philippines
GSK Investigational Site
Quezon City, 1102, Philippines
GSK Investigational Site
Cabo Rojo, Puerto Rico, 623, Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00918, Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 90660, Puerto Rico
GSK Investigational Site
Moscow, 115522, Russia
GSK Investigational Site
Moscow, 115552, Russia
GSK Investigational Site
Moscow, 117049, Russia
GSK Investigational Site
Saint Petersburg, 197022, Russia
GSK Investigational Site
Saint Petersburg, 198103, Russia
GSK Investigational Site
Seongnam-si, 463-707, South Korea
GSK Investigational Site
Seoul, 143-729, South Korea
GSK Investigational Site
Bradford, BD3 0DQ, United Kingdom
GSK Investigational Site
Derriford, Plymouth, PL6 8BX, United Kingdom
GSK Investigational Site
West of Scotland Science Park, Glasgow, G20 0XA, United Kingdom
Related Publications (1)
Gold M, Alderton C, Zvartau-Hind M, Egginton S, Saunders AM, Irizarry M, Craft S, Landreth G, Linnamagi U, Sawchak S. Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord. 2010;30(2):131-46. doi: 10.1159/000318845. Epub 2010 Aug 21.
PMID: 20733306BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2007
First Posted
January 29, 2007
Study Start
February 27, 2007
Primary Completion
September 1, 2008
Study Completion
September 5, 2008
Last Updated
May 19, 2017
Results First Posted
May 19, 2017
Record last verified: 2017-04
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.