Long-Term Nicotine Treatment of Mild Cognitive Impairment

University of Southern California35 sites in 1 country348 target enrollmentJanuary 13, 2017

ConditionsMild Cognitive Impairment

InterventionsNicotine Transdermal Patch Placebo Patch

DrugsNicotine Transdermal Patch Placebo Patch

Overview

Phase: Phase 2
Intervention: Nicotine Transdermal Patch
Conditions: Mild Cognitive Impairment
Sponsor: University of Southern California
Enrollment: 348
Locations: 35
Primary Endpoint: Cogstate Battery International Shopping List Test - Total Immediate Recall (ISLT-TIR)
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 13, 2017

End Date

September 16, 2025

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Southern California

Responsible Party

Principal Investigator

Paul S. Aisen

Professor

University of Southern California

Eligibility Criteria

Inclusion Criteria

•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.
•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)

Exclusion Criteria

•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 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.
•Clinically significant abnormalities in screening laboratories or ECG.
•Residence in skilled nursing facility.

Arms & Interventions

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

Intervention: Nicotine Transdermal Patch

Placebo Patch

190 participants will wear matching placebo patches during waking hours.

Intervention: Placebo Patch

Outcomes

Primary Outcomes

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

Time Frame: 2 years

Secondary Outcomes

Change in Baseline in Geriatric Depression Scale (GDS) to Month 25(2 years)
Change in Baseline in New York University (NYU) Paragraph Recall to Month 25(2 years)
Change from Baseline in Older Adult Self Report (OASR) / Older Adult Behavior Checklist (OABCL) 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 Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) to Month 25(2 years)
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)