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Nicotine Treatment of Mild Cognitive Impairment (MCI)

Primary Purpose

Age-Related Memory Disorders

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Transdermal nicotine patch
Placebo transdermal patch
Sponsored by
National Institute on Aging (NIA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Age-Related Memory Disorders focused on measuring Age-Related Memory Loss, Nicotine, Mild Cognitive Impairment (MCI)

Eligibility Criteria

55 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Specific Inclusion Criteria: Age 55+. Memory complaints and memory difficulties which are verified by an informant. Abnormal memory function documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised (the maximum score is 25): less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8 - 15 years of education, less than or equal to 2 for 0 - 7 years of education. Mini-Mental Status Exam score between 24 and 30 (inclusive). Clinical Dementia Rating of 0.5 with a memory box score of 0.5 or 1.0. General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit. No significant cerebrovascular disease: Modified Hachinski score of less than or equal to 4. Stable medications for at least 1 month prior to screening. Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale. Informant is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more). Adequate visual and auditory acuity to allow neuropsychological testing. Good general health with no additional diseases expected to interfere with the study. Any conditions that subject may have must be stable for 3 months prior to screening. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile). Participants will be taking no drugs with pro- or anti-cholinergic properties. Exclusion Criteria: Any significant neurologic disease such as Alzheimer's disease, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities. Major depression or another major psychiatric disorder as described in DSM-IV within the past 2 years. History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria). Any significant, unstable medical condition. Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening. Any tobacco use within the past year. Exceptions to these specific Inclusion and Exclusion Criteria (e.g., WMS-R cutoffs) may be made on a case by case basis by the Principal Investigator.

Sites / Locations

  • Georgetown University Medical Center, Department of Neurology
  • Duke University, Duke Health Center at Morreene Road
  • University of Vermont College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo Group

Active Nicotine Group

Arm Description

Placebo for first six months of study; moved to open-label active nicotine for second six months

Blinded active nicotine for first six months of study; open-label active nicotine for second six months

Outcomes

Primary Outcome Measures

Safety of transdermal nicotine patch

Secondary Outcome Measures

Change in cognitive performance
Change in global functioning

Full Information

First Posted
September 9, 2004
Last Updated
January 7, 2008
Sponsor
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT00091468
Brief Title
Nicotine Treatment of Mild Cognitive Impairment (MCI)
Official Title
Double-Blind Treatment of Mild Cognitive Impairment (MCI) With Transdermal Nicotine or Transdermal Placebo
Study Type
Interventional

2. Study Status

Record Verification Date
January 2008
Overall Recruitment Status
Unknown status
Study Start Date
September 2003 (undefined)
Primary Completion Date
July 2008 (Anticipated)
Study Completion Date
July 2008 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this 12-month study is to determine whether nicotine, administered in the form of nicotine patches, can improve symptoms of memory loss in some people experiencing mild memory problems (referred to in this study as "mild cognitive impairment" or MCI).
Detailed Description
The purpose of this study is to determine whether nicotine can improve symptoms of memory loss in some people experiencing mild memory problems (referred to in this study as "mild cognitive impairment" or MCI). The study will last approximately 12 months and will be conducted at 3 clinical sites in the United States. Recent studies have suggested that one of the causes of memory disorders may be a reduction in a particular chemical substance in the brain. This chemical substance, acetylcholine, is thought to act on certain brain cells in a specific way that helps us to remember and use memories as well as affect our mood. In MCI (and Alzheimer's disease), the level of acetylcholine may be changed, and this may impair brain functioning. Preliminary studies have suggested that short-term administration of nicotine appears to improve memory in patients with mild memory loss and early Alzheimer's disease. Nicotine imitates many of the actions of acetylcholine. By administering nicotine over a longer period of time to patients with MCI, this study could lead to a better understanding of whether nicotine can act to improve memory loss symptoms over the longer term and whether it can help delay the progression of memory loss symptoms. The amount of nicotine in each patch used in this study is the same level found in patches that are used in people who are trying to quit smoking. This study will include up to twelve visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Age-Related Memory Disorders
Keywords
Age-Related Memory Loss, Nicotine, Mild Cognitive Impairment (MCI)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Placebo for first six months of study; moved to open-label active nicotine for second six months
Arm Title
Active Nicotine Group
Arm Type
Experimental
Arm Description
Blinded active nicotine for first six months of study; open-label active nicotine for second six months
Intervention Type
Drug
Intervention Name(s)
Transdermal nicotine patch
Other Intervention Name(s)
Nicotrol
Intervention Description
double-blind phase: 5mg for 1 week, 10mg for 2 weeks, 15mg for 23 weeks open label phase: 5mg for 1 week, 10mg. for 2 weeks, 15mg. for 23 weeks taper down: 10mg. for 2 weeks, 5mg. for 1 week
Intervention Type
Drug
Intervention Name(s)
Placebo transdermal patch
Intervention Description
placebo patch, 5mg for 1 week, 10mg for 2 weeks, 15mg for 23 weeks
Primary Outcome Measure Information:
Title
Safety of transdermal nicotine patch
Time Frame
13 months
Secondary Outcome Measure Information:
Title
Change in cognitive performance
Time Frame
13 months
Title
Change in global functioning
Time Frame
13 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Specific Inclusion Criteria: Age 55+. Memory complaints and memory difficulties which are verified by an informant. Abnormal memory function documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised (the maximum score is 25): less than or equal to 8 for 16 or more years of education, less than or equal to 4 for 8 - 15 years of education, less than or equal to 2 for 0 - 7 years of education. Mini-Mental Status Exam score between 24 and 30 (inclusive). Clinical Dementia Rating of 0.5 with a memory box score of 0.5 or 1.0. General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit. No significant cerebrovascular disease: Modified Hachinski score of less than or equal to 4. Stable medications for at least 1 month prior to screening. Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale. Informant is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more). Adequate visual and auditory acuity to allow neuropsychological testing. Good general health with no additional diseases expected to interfere with the study. Any conditions that subject may have must be stable for 3 months prior to screening. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile). Participants will be taking no drugs with pro- or anti-cholinergic properties. Exclusion Criteria: Any significant neurologic disease such as Alzheimer's disease, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities. Major depression or another major psychiatric disorder as described in DSM-IV within the past 2 years. History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria). Any significant, unstable medical condition. Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening. Any tobacco use within the past year. Exceptions to these specific Inclusion and Exclusion Criteria (e.g., WMS-R cutoffs) may be made on a case by case basis by the Principal Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Newhouse, MD
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown University Medical Center, Department of Neurology
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Duke University, Duke Health Center at Morreene Road
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University of Vermont College of Medicine
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15018837
Citation
Newhouse PA, Potter A, Singh A. Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol. 2004 Feb;4(1):36-46. doi: 10.1016/j.coph.2003.11.001.
Results Reference
background
PubMed Identifier
14754447
Citation
Newhouse P, Singh A, Potter A. Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem. 2004;4(3):267-82. doi: 10.2174/1568026043451401.
Results Reference
background
PubMed Identifier
11230878
Citation
Newhouse PA, Potter A, Kelton M, Corwin J. Nicotinic treatment of Alzheimer's disease. Biol Psychiatry. 2001 Feb 1;49(3):268-78. doi: 10.1016/s0006-3223(00)01069-6. No abstract available.
Results Reference
background
Links:
URL
http://www.uvm.edu/~cnru/
Description
Nicotine Treatment of Mild Cognitive Impairment (MCI) study at University of Vermont

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Nicotine Treatment of Mild Cognitive Impairment (MCI)

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