Memory Improvement Through Nicotine Dosing (MIND) Study

NCT02720445 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: ATRI-002-NICR01AG047992131918
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 36

Brief Summary

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.

Conditions

Mild Cognitive Impairment

Keywords

Alzheimer's Disease; Nicotine; Transdermal Patch

Outcome Measures

Primary Outcomes (1)

• Cogstate Battery International Shopping List Test - Total Immediate Recall (ISLT-TIR)

  2 years

Secondary Outcomes (7)

• Change from Baseline in Mild Cognitive Impairment - Clinical Global Impression of Change (MCI-CGIC) to Month 25

  2 years

• Change from Baseline in Cogstate Brief Battery (CBB) to Month 25

  2 years

• Change in Baseline in New York University (NYU) Paragraph Recall to Month 25

  2 years

• Change from Baseline in Clinical Dementia Rating Scale (CDR) - Sum of Boxes (SOB) to Month 25

  2 years

• Change in Baseline in Geriatric Depression Scale (GDS) to Month 25

  2 years

Other Outcomes (2)

• Change from Baseline in Cerebral Spinal Fluid (CSF) Biomarkers to Month 25

  2 years

• Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Month 25

  2 years

Study Arms (2)

Nicotine Transdermal Patch

EXPERIMENTAL

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

Drug: Nicotine Transdermal Patch

Placebo Patch

PLACEBO COMPARATOR

190 participants will wear matching placebo patches during waking hours.

Drug: Placebo Patch

Interventions

Nicotine Transdermal Patch 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.

Nicotine Transdermal Patch

Placebo Patch DRUG

Matching placebo patches worn during waking hours.

Placebo Patch

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have a subjective memory concern as reported by participant, study partner, or clinician
• 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
• Mini-Mental State Exam score between 24 and 30, inclusive
• Clinical Dementia Rating (CDR) Global = 0.5. Memory Box score must be at least 0.5
• 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
• Age 55-90 (inclusive)
• 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
• Geriatric Depression Scale score of less than or equal to 14
• 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
• Adequate visual and auditory acuity to allow neuropsychological testing
• Good general health with no additional diseases/disorders expected to interfere with the study

You may not qualify if:

• 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.).
• 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.
• 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
• History of schizophrenia (DSM V criteria)
• History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
• 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.
• 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
• Clinically significant abnormalities in screening laboratories or ECG.
• Residence in skilled nursing facility.
• 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.
• For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT (partial thromboplastin time) at screening
• For MRI sub-study participants, contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.
• Patients whom the Site PI deems to be otherwise ineligible.

Sponsors & Collaborators

• University of Southern California: lead
• National Institute on Aging (NIA): collaborator
• Vanderbilt University: collaborator
• Alzheimer's Therapeutic Research Institute: collaborator

Study Sites (36)

Perseverance Research Center

Scottsdale, Arizona, 85254, United States

Location

Central Arkansas Veterans Healthcare System

North Little Rock, Arkansas, 72205, United States

Location

USC Rancho Los Amigos

Downey, California, 90242, United States

Location

Sharp Neurocognitive Research Center

San Diego, California, 92123, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

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

Danbury, Connecticut, 06810, United States

Location

Georgetown University

Washington D.C., District of Columbia, 200072145, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Brain Matters Research

Stuart, Florida, 34997, United States

Location

Augusta University Movement and Memory Disorders

Augusta, Georgia, 30912, United States

Location

Velocity Clinical Research - Boise

Meridian, Idaho, 83642, United States

Location

Northwestern University

Chicago, Illinois, 606113010, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Headlands Eastern MA LLC

Plymouth, Massachusetts, 02360, United States

Location

University at Buffalo (UBMD)

Buffalo, New York, 14203, United States

Location

Velocity Clinical Research - Syracuse

East Syracuse, New York, 13057, United States

Location

New York University Medical Center

New York, New York, 100166055, United States

Location

Mount Sinai School of Medicine

New York, New York, 100296552, United States

Location

Integrative Clinical Trials

New York, New York, 11229, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Central States Research (formerly Tulsa Clinical Research)

Tulsa, Oklahoma, 74104, United States

Location

Providence Brain and Spine Institute

Portland, Oregon, 97225, United States

Location

LeHigh Valley Hospital

Allentown, Pennsylvania, 18105, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, 294011113, United States

Location

Neurology Clinic, P.C.

Cordova, Tennessee, 38018, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Glenn Biggs Institute at the University of Texas Health

San Antonio, Texas, 78229, United States

Location

University of Washington Memory and Brain Wellness Center

Seattle, Washington, 98195, United States

Location

Kingfisher Cooperative, LLC

Spokane, Washington, 99202, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

Related Publications (6)

• 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.

  PMID: 8024677 BACKGROUND

• 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.

  PMID: 22232050 BACKGROUND

• 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.

  PMID: 16482084 BACKGROUND

• 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.

  PMID: 17700646 BACKGROUND

• 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.

  PMID: 3137593 BACKGROUND

• 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.

  PMID: 31810978 DERIVED

Related Links

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

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Paul Aisen, MD

  USC Alzheimer's Therapeutic Research Institute (ATRI)

  STUDY DIRECTOR

• Paul Newhouse, MD

  Vanderbilt University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: March 25, 2016
• Study Start: January 13, 2017
• Primary Completion: August 25, 2025
• Study Completion: September 16, 2025
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (36)