Nicotine Treatment of Mild Cognitive Impairment (MCI)

• ClinicalTrials.gov Identifier: NCT00091468
• Recruitment Status: Unknown
• First Posted: October 14, 2004
• Last Update Posted: January 15, 2008
• Sponsor: National Institute on Aging (NIA)
• Information provided by: National Institute on Aging (NIA)

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).

Condition or disease	Intervention/treatment	Phase
Age-Related Memory Disorders	Drug: Transdermal nicotine patch; Drug: Placebo transdermal patch	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-Blind Treatment of Mild Cognitive Impairment (MCI) With Transdermal Nicotine or Transdermal Placebo
• Study Start Date: September 2003
• Estimated Primary Completion Date: July 2008
• Estimated Study Completion Date: July 2008

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo Group; Placebo for first six months of study; moved to open-label active nicotine for second six months	Drug: Placebo transdermal patch; placebo patch, 5mg for 1 week, 10mg for 2 weeks, 15mg for 23 weeks
Experimental: Active Nicotine Group; Blinded active nicotine for first six months of study; open-label active nicotine for second six months	Drug: Transdermal nicotine patch; 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; Other Name: Nicotrol

Outcome Measures

Primary Outcome Measures :

1. Safety of transdermal nicotine patch [ Time Frame: 13 months ]

Secondary Outcome Measures :

1. Change in cognitive performance [ Time Frame: 13 months ]
2. Change in global functioning [ Time Frame: 13 months ]

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

  1. less than or equal to 8 for 16 or more years of education,
  2. less than or equal to 4 for 8 - 15 years of education,
  3. 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.

Contacts and Locations

Locations

United States, District of Columbia

Georgetown University Medical Center, Department of Neurology

Washington, District of Columbia, United States, 20057

United States, North Carolina

Duke University, Duke Health Center at Morreene Road

Durham, North Carolina, United States, 27705

United States, Vermont

University of Vermont College of Medicine

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Paul Newhouse, MD; University of Vermont

More Information

Additional Information:

Nicotine Treatment of Mild Cognitive Impairment (MCI) study at University of Vermont 

Publications:

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.

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.

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.

• Responsible Party: Paul Newhouse, M.D., University of Vermont
• ClinicalTrials.gov Identifier: NCT00091468
• Other Study ID Numbers: IA0060; R01AG022462-02 ( U.S. NIH Grant/Contract )
• First Posted: October 14, 2004
• Last Update Posted: January 15, 2008
• Last Verified: January 2008

Keywords provided by National Institute on Aging (NIA):

Age-Related Memory Loss; Nicotine; Mild Cognitive Impairment (MCI)

Additional relevant MeSH terms:

Memory Disorders; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action