Clinical trial NCT00428090: Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: apolipoprotein E
monotherapy
cognition
mild
rosiglitazone
Alzheimer's disease
moderate
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-01-29
Enrollment: 862
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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 e4-stratified subjects with mild to moderate Alzheimer's disease. (REFLECT-1)

Eligibility criteria: Inclusion criteria:

* 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.

Exclusion criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: Baseline (W0) and W24
measure: 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
timeFrame: Baseline (W0) and W24
measure: Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
timeFrame: Baseline (W0) and W24
measure: Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in APOE4 Negative Cohort
timeFrame: Baseline (W0) and W24
measure: 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
timeFrame: Baseline (W0) and W24
measure: Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
timeFrame: Baseline (W0) and W24
Secondary outcomes:
measure: Change From Baseline (W0) in Mean ADAS-Cog Total Score at W8, W16, W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W8, W16, W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean Neuropsychiatric Inventory (NPI) Total Score at W8, W16, W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean Disability Assessment for Dementia (DAD) Scale Total Score at W8, W16, W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean Short Term Memory Assessment Total Score (ADAS-Cog Q1 Plus Q7) at W8, W16, W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Utility
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Thermometer (Visual Analog Scale [VAS])
timeFrame: Baseline (W0) and up to W24
measure: Time Spent Caring for Basic and Instrumental Activities Resource Utilization in Dementia (RUD) Scale at W12 and W24
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score at W12 and W24.
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Mini Mental State Examination (MMSE) Total Score at W24.
timeFrame: Baseline (W0) and W24
measure: Change From Baseline (W0) in Glycosylated Hemoglobin (HbA1c) at W24.
timeFrame: Baseline (W0) and W24
measure: Number of Participants With Adverse Events Defined by Severity
timeFrame: Up to W24
measure: Number of Participants With Systolic and Diastolic Blood Pressure (SBP and DBP), Heart Rate (HR) and Weight Values of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT).
timeFrame: Up to W24
measure: Change From Baseline (W0) in 12-lead Electrocardiogram (ECG)
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Heart Rate (HR) Measured From 12-lead Electrocardiogram (ECG)
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Body Weight
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Hemoglobin
timeFrame: Baseline (W0) and up to W24
measure: Change From Baseline (W0) in Hematocrit
timeFrame: Baseline (W0) and Up to W24
measure: Change From Baseline (W0) in Periodic HbA1c Assessment
timeFrame: Baseline (W0) and up to W24
measure: Number of Par. With Hematology Data of Potential Clinical Concern Any Time on Treatment
timeFrame: Up to W24
measure: Number of Par. With Clinical Chemistry Values of Potential Clinical Concern Any Time on Treatment
timeFrame: Up to W24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Palo Alto
country: United States
facility: GSK Investigational Site
state: California
city: Reseda
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Fairfield
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Deerfield Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Delray Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Destin
country: United States
facility: GSK Investigational Site
state: Florida
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Melbourne
country: United States
facility: GSK Investigational Site
state: Florida
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: Sunrise
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: St. Paul
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Kenilworth
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Toms River
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Centerville
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Toledo
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Jenkintown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: DeSoto
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Middleton
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Graz-Eggenberg
country: Austria
facility: GSK Investigational Site
city: Hall in Tirol
country: Austria
facility: GSK Investigational Site
city: Linz
country: Austria
facility: GSK Investigational Site
city: Linz
country: Austria
facility: GSK Investigational Site
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Providencia / Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Puente Alto - Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: Dubrovnik
country: Croatia
facility: GSK Investigational Site
city: Zagreb
country: Croatia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Ellwangen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Guenzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Nuernberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Unterhaching
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bad Homburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Achim
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Baesweiler
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bielefeld
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Duisburg
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Juelich
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Itzehoe
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Gera
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Melissia
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Gyula
country: Hungary
facility: GSK Investigational Site
city: Kaposvár
country: Hungary
facility: GSK Investigational Site
city: Pécs
country: Hungary
facility: GSK Investigational Site
city: Szeged
country: Hungary
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Nagpur
country: India
facility: GSK Investigational Site
city: Tirupati
country: India
facility: GSK Investigational Site
city: Seongnam-si,
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Saltillo
country: Mexico
facility: GSK Investigational Site
state: Coahuila
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: Auckland
country: New Zealand
facility: GSK Investigational Site
city: Karachi
country: Pakistan
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Pasig City
country: Philippines
facility: GSK Investigational Site
city: Quezon City
country: Philippines
facility: GSK Investigational Site
city: Cabo Rojo
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Derriford, Plymouth
country: United Kingdom
facility: GSK Investigational Site
city: West of Scotland Science Park, Glasgow
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.