Memory Improvement Through Nicotine Dosing (MIND) Study

NCT ID: NCT02720445

Last Updated: 2025-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

348 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-13

Study Completion Date

2025-09-16

Brief Summary

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The purpose of the study is to see if daily transdermal nicotine is able to produce a significant cognitive, clinical and functional improvement in participants with MCI. Neuronal nicotinic receptors have long been known to play a critical role in memory function in preclinical studies, with nicotine improving attention, learning, and memory function.

The study will enroll 380 participants for a 2 year period. Participants will be randomized (50:50) to either the transdermal nicotine, beginning at 7mg/day, and increasing to 21mg/day, or placebo skin patch.

Detailed Description

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Conditions

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Mild Cognitive Impairment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Nicotine Transdermal Patch

190 participants will wear nicotine transdermal patches during waking hours. Active dose will titrate up from 3.5mg to 21mg in the first 6 weeks of treatment, remain at 21mg for 22.5 months, and then taper down in the final month of treatment

Group Type EXPERIMENTAL

Nicotine Transdermal Patch

Intervention Type DRUG

21mg Nicotine transdermal patches worn during waking hours. Active dose will titrate up from 3.5mg to 21mg in the first 6 weeks of treatment, remain at 21mg for 22.5 months, and then taper down in the final month of treatment.

Placebo Patch

190 participants will wear matching placebo patches during waking hours.

Group Type PLACEBO_COMPARATOR

Placebo Patch

Intervention Type DRUG

Matching placebo patches worn during waking hours.

Interventions

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Nicotine Transdermal Patch

21mg Nicotine transdermal patches worn during waking hours. Active dose will titrate up from 3.5mg to 21mg in the first 6 weeks of treatment, remain at 21mg for 22.5 months, and then taper down in the final month of treatment.

Intervention Type DRUG

Placebo Patch

Matching placebo patches worn during waking hours.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician
2. Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised:

* less than or equal to 11 for 16 or more years of education
* less than or equal to 9 for 8 - 15 years of education
* less than or equal to 6 for 0 - 7 years of education
3. Mini-Mental State Exam score between 24 and 30, inclusive
4. Clinical Dementia Rating (CDR) Global = 0.5. Memory Box score must be at least 0.5
5. General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease dementia cannot be made by the site physician at the time of the screening visit
6. Age 55-90 (inclusive)
7. Stable permitted medications for 4 weeks or longer as specified in Section 6, including:

• Memantine and cholinesterase inhibitors are allowable if stable for 12 weeks prior to screen
8. Geriatric Depression Scale score of less than or equal to 14
9. Study Partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to most visits to answer questions about the participant
10. Adequate visual and auditory acuity to allow neuropsychological testing
11. Good general health with no additional diseases/disorders expected to interfere with the study
12. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
13. Completed six grades of education or has a good work history
14. Fluent in English or Spanish

Exclusion Criteria

1. Regular use of tobacco products within the past year, such as smoking (cigarettes, pipes, cigars, etc.) or use of other nicotine products (chewing tobacco, e-cigarettes, nicotine patches, gum, sprays, etc.).
2. Any significant neurologic disease such as Alzheimer's disease dementia, 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.
3. Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol
4. History of schizophrenia (DSM V criteria)
5. History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
6. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
7. Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
8. Clinically significant abnormalities in B12 or TFTs (Thyroid Function Tests) that might interfere with the study. A low B12 is exclusionary, unless the required follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
9. Clinically significant abnormalities in screening laboratories or ECG.
10. Residence in skilled nursing facility.
11. Use of any excluded medication as described in the protocol, including:

* Use of centrally acting anti-cholinergic drugs
* Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening.
12. For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT (partial thromboplastin time) at screening
13. For MRI sub-study participants, contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.
14. Patients whom the Site PI deems to be otherwise ineligible.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Vanderbilt University

OTHER

Sponsor Role collaborator

Alzheimer's Therapeutic Research Institute

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Paul S. Aisen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Paul Aisen, MD

Role: STUDY_DIRECTOR

USC Alzheimer's Therapeutic Research Institute (ATRI)

Paul Newhouse, MD

Role: STUDY_DIRECTOR

Vanderbilt University

Locations

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Perseverance Research Center

Scottsdale, Arizona, United States

Site Status

Central Arkansas Veterans Healthcare System

North Little Rock, Arkansas, United States

Site Status

USC Rancho Los Amigos

Downey, California, United States

Site Status

Sharp Neurocognitive Research Center

San Diego, California, United States

Site Status

Syrentis Clinical Research

Santa Ana, California, United States

Site Status

Nuvance Health Medical Practice Ct, Inc.; Associated Neurologists, PC

Danbury, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

JEM Research Institute

Atlantis, Florida, United States

Site Status

Brain Matters Research

Delray Beach, Florida, United States

Site Status

Miami Jewish Health Systems

Miami, Florida, United States

Site Status

Brain Matters Research

Stuart, Florida, United States

Site Status

Augusta University Movement and Memory Disorders

Augusta, Georgia, United States

Site Status

Velocity Clinical Research - Boise

Meridian, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Headlands Eastern MA LLC

Plymouth, Massachusetts, United States

Site Status

University at Buffalo (UBMD)

Buffalo, New York, United States

Site Status

Velocity Clinical Research - Syracuse

East Syracuse, New York, United States

Site Status

New York University Medical Center

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Integrative Clinical Trials

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Central States Research (formerly Tulsa Clinical Research)

Tulsa, Oklahoma, United States

Site Status

Providence Brain and Spine Institute

Portland, Oregon, United States

Site Status

LeHigh Valley Hospital

Allentown, Pennsylvania, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, United States

Site Status

Neurology Clinic, P.C.

Cordova, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Houston Methodist Neurological Institute

Houston, Texas, United States

Site Status

Glenn Biggs Institute at the University of Texas Health

San Antonio, Texas, United States

Site Status

University of Washington Memory and Brain Wellness Center

Seattle, Washington, United States

Site Status

Kingfisher Cooperative, LLC

Spokane, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Newhouse PA, Potter A, Corwin J, Lenox R. Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior. Neuropsychopharmacology. 1994 Apr;10(2):93-107. doi: 10.1038/npp.1994.11.

Reference Type BACKGROUND
PMID: 8024677 (View on PubMed)

Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, Pfaff A, Wilkins H, Howard D, Levin ED. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology. 2012 Jan 10;78(2):91-101. doi: 10.1212/WNL.0b013e31823efcbb.

Reference Type BACKGROUND
PMID: 22232050 (View on PubMed)

Dumas J, Hancur-Bucci C, Naylor M, Sites C, Newhouse P. Estrogen treatment effects on anticholinergic-induced cognitive dysfunction in normal postmenopausal women. Neuropsychopharmacology. 2006 Sep;31(9):2065-78. doi: 10.1038/sj.npp.1301042. Epub 2006 Feb 15.

Reference Type BACKGROUND
PMID: 16482084 (View on PubMed)

Newhouse PA, Dumas J, Hancur-Bucci C, Naylor M, Sites CK, Benkelfat C, Young SN. Estrogen administration negatively alters mood following monoaminergic depletion and psychosocial stress in postmenopausal women. Neuropsychopharmacology. 2008 Jun;33(7):1514-27. doi: 10.1038/sj.npp.1301530. Epub 2007 Aug 15.

Reference Type BACKGROUND
PMID: 17700646 (View on PubMed)

Newhouse PA, Sunderland T, Tariot PN, Blumhardt CL, Weingartner H, Mellow A, Murphy DL. Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology (Berl). 1988;95(2):171-5. doi: 10.1007/BF00174504.

Reference Type BACKGROUND
PMID: 3137593 (View on PubMed)

Joe E, Ringman JM. Cognitive symptoms of Alzheimer's disease: clinical management and prevention. BMJ. 2019 Dec 6;367:l6217. doi: 10.1136/bmj.l6217.

Reference Type DERIVED
PMID: 31810978 (View on PubMed)

Related Links

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http://keck.usc.edu/atri/research/studies/

Alzheimer's Therapeutic Research Institute (ATRI). ATRI is the Coordinating Center for the MIND study.

http://mindstudy.org/

MIND study public website

Other Identifiers

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R01AG047992

Identifier Type: NIH

Identifier Source: secondary_id

View Link

131918

Identifier Type: OTHER

Identifier Source: secondary_id

ATRI-002-NIC

Identifier Type: -

Identifier Source: org_study_id

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