Principal Investigator: Scott Langenecker
Keywords: nicotine , mild , cognitive , impairment Department: Psychiatry-Psychologists
IRB Number: 00106309
Specialty: Neuropsychology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Anna Bradford
anna.bradford@hsc.utah.edu
8015859450

Brief Summary

This study is a multi-site clinical trial of the safety and efficacy of transdermal nicotine in alleviating symptoms of MCI, designed to test the hypothesis that nicotinic cholinergic receptor stimulation reliably produces enhancement in attentional functioning and memory. If the hypotheses are validated, these findings will support a novel, broadly available, and inexpensive repurposed intervention for MCI.

The trial will consist of 24 months (plus a 3 week tapering off period) of randomized double-blind placebo-controlled treatment with nicotine or placebo in approximately 300 participants with MCI (150 per arm). This would be the longest trial of nicotine or nicotinic agonists to date and if successful would lead to combined trials with other symptomatic agents and/or agents that might directly interact with Aβ or tau-related mechanisms. Success of the pilot trial is encouraging and justifies cautious but significant optimism for sustained success in this proposed study.

 

Inclusion Criteria

Participants must meet the following 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 clinician 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 6.10,
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. Must speak English fluently

Exclusion Criteria

Participants must not meet the following criteria:
1. Any use of tobacco or nicotine 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 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 a skilled nursing facility.

11. Use of any excluded medication as described in Section 6.10, including:
• Use 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 at screening

13. For MRI sub-study participants, contraindications for MRI studies, including
claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac
pacemaker.

14. Participants whom the Site PI deems to be otherwise ineligible.