Memory Improvement Through Nicotine Dosing (MIND) Study

Mild Cognitive Impairment Clinical Trial

— MIND  

Official title:

Long-Term Nicotine Treatment of Mild Cognitive Impairment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02720445
• Other study ID #: ATRI-002-NIC
• Secondary ID: R01AG04799213191
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 13, 2017
• Est. completion date: August 2025

Study information

• Verified date: December 2023
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 380
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• 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.
• Placebo Patch
Matching placebo patches worn during waking hours.

Locations

Country	Name	City	State
United States	LeHigh Valley Hospital	Allentown	Pennsylvania
United States	JEM Research Institute	Atlantis	Florida
United States	Augusta University Movement and Memory Disorders	Augusta	Georgia
United States	University at Buffalo (UBMD)	Buffalo	New York
United States	Ralph H. Johnson VA Health Care System	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Neurology Clinic, P.C.	Cordova	Tennessee
United States	Nuvance Health Medical Practice Ct, Inc.; Associated Neurologists, PC	Danbury	Connecticut
United States	Brain Matters Research	Delray Beach	Florida
United States	USC Rancho Los Amigos	Downey	California
United States	Velocity Clinical Research - Syracuse	East Syracuse	New York
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Wisconsin	Madison	Wisconsin
United States	Velocity Clinical Research - Boise	Meridian	Idaho
United States	Miami Jewish Health Systems	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Integrative Clinical Trials	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	New York University Medical Center	New York	New York
United States	Central Arkansas Veterans Healthcare System	North Little Rock	Arkansas
United States	Headlands Eastern MA LLC	Plymouth	Massachusetts
United States	Providence Brain and Spine Institute	Portland	Oregon
United States	Glenn Biggs Institute at the University of Texas Health	San Antonio	Texas
United States	Sharp Neurocognitive Research Center	San Diego	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	Perseverance Research Center	Scottsdale	Arizona
United States	University of Washington Memory and Brain Wellness Center	Seattle	Washington
United States	Kingfisher Cooperative, LLC	Spokane	Washington
United States	Brain Matters Research	Stuart	Florida
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Central States Research (formerly Tulsa Clinical Research)	Tulsa	Oklahoma
United States	Georgetown University	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern California	Alzheimer's Therapeutic Research Institute, National Institute on Aging (NIA), Vanderbilt University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from Baseline in Cerebral Spinal Fluid (CSF) Biomarkers to Month 25	CSF will be performed in approximately 50 participants each	2 years
Other	Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Month 25		2 years
Primary	Change from Baseline of the Conners Continuous Performance Task (CPT) to Month 25		2 years
Secondary	Change from Baseline in Mild Cognitive Impairment - Clinical Global Impression of Change (MCI-CGIC) to Month 25	The MCI-CGIC is the MCI version of the clinician's global impression of change. In this trial it will measure change in the participant's condition between the baseline visit and subsequent visits.	2 years
Secondary	Change from Baseline in Cogstate Brief Battery (CBB) to Month 25	This battery will be used for the purpose of assessing the cognitive status of the participants and will assist in documenting multiple domains of cognitive impairment.	2 years
Secondary	Change in Baseline in New York University (NYU) Paragraph Recall to Month 25	This test measures immediate and delayed verbal recall of a brief story.	2 years
Secondary	Change from Baseline in Clinical Dementia Rating Scale (CDR) - Sum of Boxes (SOB) to Month 25	The is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe.	2 years
Secondary	Change in Baseline in Geriatric Depression Scale (GDS) to Month 25	This is a 30-item self-report assessment used to identify depression in the elderly.	2 years
Secondary	Change in Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) to Month 25	This scale is an inventory developed to assess functional performance in participantss with Alzheimer's disease.	2 years
Secondary	Change from Baseline in Older Adult Self Report (OASR) / Older Adult Behavior Checklist (OABCL) to Month 25	The OASR/OABCL is a general index of psychopathologic symptoms and signs that is specifically relevant to elderly individuals and is developmentally appropriate, covers a wide range of psychopathologic signs and symptoms, and functional measures. It allows multi-informant perspective (both patient and informant). The items are focused on common elderly emotional, functional, or medical problems. The OASR is completed by the participant and the companion OABCL is completed by the informant.	2 years

External Links

•   Alzheimer's Disease Education and Referral (ADEAR) Center. The ADEAR Center is a service of the National Institute on Aging (NIA).
•   Alzheimer's Therapeutic Research Institute (ATRI). ATRI is the Coordinating Center for the MIND study.
•   MIND study public website