search
Back to results

Rosiglitazone Effects on Cognition for Adults in Later Life (RECALL)

Primary Purpose

Mild Cognitive Impairment

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rosiglitazone
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring cognition disorders, Alzheimer's disease, memory

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: MCI diagnosis: Participants will be diagnosed with MCI by consensus of a team of physicians and neuropsychologists experienced in the diagnosis of MCI, using the Petersen (Petersen, 1999, 2001) criteria for amnestic MCI or multiple domain MCI with amnestic features: a) the presence of subjective memory complaints, evaluated via detailed patient history and informant interview, b) objective verification of memory impairment as measured by neuropsychological tests, c) normal general cognitive function, d) intact or only mildly impaired activities of daily living, and e) absence of dementia per NINCDS/ADRDA and/or DSM-IV criteria Exclusion Criteria: The following exclusion criteria will be used, based on initial physical examination, medical history, lab work, and oral glucose tolerance test (OGTT) results: Diagnosis of diabetes or other relevant glucoregulatory disorders Use of any oral anti-diabetic compounds Clinically significant elevations in liver function Significant neurological disease that might affect cognition, other than MCI, including Alzheimer's disease, large-vessel stroke, Parkinson's disease, multiple sclerosis, recent severe head injury (loss of consciousness for more than 30 minutes in the past year), or remote head injury resulting in permanent cognitive or neurological sequelae History or current evidence of congestive heart failure (CHF) History of documented ischemic cardiac disease, i.e., angina, MI, angioplasty, stent, or CABG History of cardiac or vascular surgery, or significant arrhythmia within the last year; or planned major intervention such as cardiac surgery or stenting. A history of cardiac surgery for non-ischemic indications (i.e., valve repair or replacement) greater than one year prior to enrollment is not exclusionary if all other criteria are met Significant ECG abnormalities including heart rate less than 50 or greater than 100 beats per minute (dependent upon the individual's general health); any previously unrecognized arrhythmia requiring further intervention Significant peripheral edema at the time of screening Significant medical illness or organ failure, including but not limited to renal disease, hepatic disease, and unstable cardiac disease Regular current use of antipsychotic, anticonvulsive, anxiolytic, or sedative medications; antidepressant medications are not exclusionary, provided the individual does not have current major depression A current diagnosis of major depression or other significant psychiatric comorbidity Clinically significant anemia at the time of screening Fasting triglyceride level greater than 400 Fasting glucose 125 or greater, or two-hour glucose value greater than 199 during the OGTT; participants will be notified if their fasting blood sugar (monitored every 3 months) exceeds 125, and they will be withdrawn from further participation if their fasting blood sugar exceeds 125 for two consecutive months For the MRI substudy, additional exclusion criteria include 1) previous exposure to work involving the cutting or grinding of metal, 2) the presence of a pacemaker, aneurysm clip, or other implanted metal device that would prohibit MRI procedures, and 3) significant history of claustrophobia

Sites / Locations

  • Banner Alzheimer Institute
  • UCLA Alzheimer's Disease Center
  • University of Washington/VA Puget Sound Health Care System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

A

B

Arm Description

oral rosiglitazone 4 mg twice daily for 18 months

placebo pill twice daily for 18 months

Outcomes

Primary Outcome Measures

Cognitive measures: delayed list recall, Stroop Interference test
Biological outcomes: plasma insulin, IDE, AB40, AB42, inflammatory cytokines, and F2-isoprostanes
MRI outcome: Whole brain and medial temporal lobe atrophy rate

Secondary Outcome Measures

Cognitive measures: ADAS-cog total score, story recall verbal fluency, paired associate learning, SOPT, rating scales

Full Information

First Posted
October 19, 2005
Last Updated
August 4, 2011
Sponsor
University of Washington
Collaborators
National Institute on Aging (NIA), GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT00242593
Brief Title
Rosiglitazone Effects on Cognition for Adults in Later Life
Acronym
RECALL
Official Title
The Effects of Rosiglitazone on Cognition in Patients With MCI
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Unknown status
Study Start Date
June 2006 (undefined)
Primary Completion Date
December 2011 (Anticipated)
Study Completion Date
December 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
University of Washington
Collaborators
National Institute on Aging (NIA), GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the effects of the insulin-sensitizing medication rosiglitazone on attention and memory skills in older adults with mild cognitive impairment (MCI). The study also will examine the effects of this medication on brain structures that support memory and other thinking abilities, and on biological markers associated with inflammation, insulin resistance, and cardiovascular disease.
Detailed Description
The study will examine the effects of the insulin-sensitizing agent rosiglitazone on learning and memory for 120 patients diagnosed with MCI. Participants will be randomized to an 18-month trial of rosiglitazone or placebo, followed by a 2-month washout period. At screening and at treatment month 18, all participants will undergo an oral glucose tolerance test (OGTT) to estimate pre- and post- treatment insulin sensitivity and β-cell function. Cognitive measures and blood samples for biochemical assays will be obtained at baseline, treatment months 6, 12, and 18, and washout (two months after completing treatment). During treatment, participants will have safety labs drawn and receive physical assessment of any adverse events, changes in health status, or changes in medication; initially these visits will be done at weeks 2 and 4, and then every three months. For months in which a safety visit is not scheduled, telephone monitoring to assess any health concerns will be conducted. All participants enrolled in the primary study will be approached to participate in an MRI substudy; patients will undergo serial brain MRI before treatment and following 18 months of rosiglitazone or placebo, using three-dimensional T1-weighted images. Comparison of MCI patients receiving rosiglitazone and placebo will be conducted to determine whether the rate of medial temporal lobe (MTL) and whole brain atrophy is altered following treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment
Keywords
cognition disorders, Alzheimer's disease, memory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
oral rosiglitazone 4 mg twice daily for 18 months
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
placebo pill twice daily for 18 months
Intervention Type
Drug
Intervention Name(s)
Rosiglitazone
Other Intervention Name(s)
Avandia
Intervention Description
4 mg twice daily oral rosiglitazone or placebo pill for 18 months
Primary Outcome Measure Information:
Title
Cognitive measures: delayed list recall, Stroop Interference test
Time Frame
every 6 months for 18 months, again 2 at months post-treatment (20 months)
Title
Biological outcomes: plasma insulin, IDE, AB40, AB42, inflammatory cytokines, and F2-isoprostanes
Time Frame
every 6 months for 18 months, again 2 at months post-treatment (20 months)
Title
MRI outcome: Whole brain and medial temporal lobe atrophy rate
Time Frame
baseline and 18 months
Secondary Outcome Measure Information:
Title
Cognitive measures: ADAS-cog total score, story recall verbal fluency, paired associate learning, SOPT, rating scales
Time Frame
every 6 months for 18 months, again 2 at months post-treatment (20 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: MCI diagnosis: Participants will be diagnosed with MCI by consensus of a team of physicians and neuropsychologists experienced in the diagnosis of MCI, using the Petersen (Petersen, 1999, 2001) criteria for amnestic MCI or multiple domain MCI with amnestic features: a) the presence of subjective memory complaints, evaluated via detailed patient history and informant interview, b) objective verification of memory impairment as measured by neuropsychological tests, c) normal general cognitive function, d) intact or only mildly impaired activities of daily living, and e) absence of dementia per NINCDS/ADRDA and/or DSM-IV criteria Exclusion Criteria: The following exclusion criteria will be used, based on initial physical examination, medical history, lab work, and oral glucose tolerance test (OGTT) results: Diagnosis of diabetes or other relevant glucoregulatory disorders Use of any oral anti-diabetic compounds Clinically significant elevations in liver function Significant neurological disease that might affect cognition, other than MCI, including Alzheimer's disease, large-vessel stroke, Parkinson's disease, multiple sclerosis, recent severe head injury (loss of consciousness for more than 30 minutes in the past year), or remote head injury resulting in permanent cognitive or neurological sequelae History or current evidence of congestive heart failure (CHF) History of documented ischemic cardiac disease, i.e., angina, MI, angioplasty, stent, or CABG History of cardiac or vascular surgery, or significant arrhythmia within the last year; or planned major intervention such as cardiac surgery or stenting. A history of cardiac surgery for non-ischemic indications (i.e., valve repair or replacement) greater than one year prior to enrollment is not exclusionary if all other criteria are met Significant ECG abnormalities including heart rate less than 50 or greater than 100 beats per minute (dependent upon the individual's general health); any previously unrecognized arrhythmia requiring further intervention Significant peripheral edema at the time of screening Significant medical illness or organ failure, including but not limited to renal disease, hepatic disease, and unstable cardiac disease Regular current use of antipsychotic, anticonvulsive, anxiolytic, or sedative medications; antidepressant medications are not exclusionary, provided the individual does not have current major depression A current diagnosis of major depression or other significant psychiatric comorbidity Clinically significant anemia at the time of screening Fasting triglyceride level greater than 400 Fasting glucose 125 or greater, or two-hour glucose value greater than 199 during the OGTT; participants will be notified if their fasting blood sugar (monitored every 3 months) exceeds 125, and they will be withdrawn from further participation if their fasting blood sugar exceeds 125 for two consecutive months For the MRI substudy, additional exclusion criteria include 1) previous exposure to work involving the cutting or grinding of metal, 2) the presence of a pacemaker, aneurysm clip, or other implanted metal device that would prohibit MRI procedures, and 3) significant history of claustrophobia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Craft, PhD
Organizational Affiliation
University of Washington/VA Puget Sound Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner Alzheimer Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
UCLA Alzheimer's Disease Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Washington/VA Puget Sound Health Care System
City
Seattle/Tacoma
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
10954962
Citation
Goldstein BJ. Rosiglitazone. Int J Clin Pract. 2000 Jun;54(5):333-7.
Results Reference
background
PubMed Identifier
11160777
Citation
Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: The glitazones or insulin sensitizers. Annu Rev Med. 2001;52:239-57. doi: 10.1146/annurev.med.52.1.239.
Results Reference
background
PubMed Identifier
14568809
Citation
Lopez OL, Jagust WJ, Dulberg C, Becker JT, DeKosky ST, Fitzpatrick A, Breitner J, Lyketsos C, Jones B, Kawas C, Carlson M, Kuller LH. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. Arch Neurol. 2003 Oct;60(10):1394-9. doi: 10.1001/archneur.60.10.1394.
Results Reference
background
PubMed Identifier
11306609
Citation
Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001 Apr 15;21(8):2561-70. doi: 10.1523/JNEUROSCI.21-08-02561.2001.
Results Reference
background
PubMed Identifier
12467491
Citation
Watson GS, Craft S. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs. 2003;17(1):27-45. doi: 10.2165/00023210-200317010-00003.
Results Reference
background

Learn more about this trial

Rosiglitazone Effects on Cognition for Adults in Later Life

We'll reach out to this number within 24 hrs