Nicotine Treatment of Cognitive Decline in Down Syndrome

• Status: Completed
• Trial end date: 2021-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will ascertain whether nicotine is safe and tolerable in DS patients, help with dose-ranging of nicotine in DS, look for evidence of enhancements in cognitive functioning, and establish evidence for biological and behavioral correlates of nicotinic stimulation effects. The knowledge gained from the translational aspects of this project may also guide the application of new nicotinic drugs in DS and generate, for the first time, data on the importance of nicotinic receptor changes in the development of cognitive impairment in DS adults.

Hypotheses:

• Transdermal nicotine treatment will be well tolerated out to one month by non-smoking DS patients without significant adverse effects.

• Nicotine will enhance cognitive performance by one month compared to baseline and post-treatment testing.

• Nicotine will enhance functioning detectable by clinician and/or informant ratings (pre-post).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University; Vanderbilt University Medical Center
• Treatments: Nicotine

Criteria

Inclusion Criteria:

• Cognitive complaints and/or memory difficulties which are verified as new onset by an informant.

• Cognitive Global Rating consistent with mild impairment or deterioration from premorbid baseline.

• General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease/dementia cannot be made by the physician at the time of the screening visit.

• No significant cerebrovascular disease: Modified Hachinski score of less than or equal to 4.

• Age 25+.

• Stable medications for at least 1 month prior to screening. Central nervous system (CNS) medications should be stable for 3 months.

• No evidence of major depression.

• Informant is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more).

• Adequate visual and auditory acuity to allow neuropsychological testing.

• Good general health with no additional diseases expected to interfere with the study.

• Normal B12, rapid plasma reagin (RPR), and Thyroid Function Tests or without any clinically significant abnormalities that would be expected to interfere with the study.

• ECG without clinically significant abnormalities that would be expected to interfere with the study.

• Subject is not pregnant, lactating.

• Subjects will be taking no drugs with cholinergic properties (e.g donepezil).

• Agreement not to take other vitamin or supplements other than multivitamins.

• Negative urine pregnancy test in females.

Exclusion Criteria:

• Any significant neurologic disease such as Alzheimer's disease, 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.

• Active Major depression or another major psychiatric disorder as described in DSM-IV.

• History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).

• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including:

• History of myocardial infarction in the past year or unstable or severe cardiovascular disease including angina or congestive heart failure (CHF) with symptoms at rest.

• Clinically significant obstructive pulmonary disease or asthma.

• Clinically significant and unstable gastrointestinal disorder such as ulcer disease or a history of active or occult gastrointestinal bleeding within two years.

• Clinically significant laboratory test abnormalities on the battery of screening tests (hematology, chemistry, urinalysis, ECG).

• Insulin-requiring diabetes or uncontrolled diabetes mellitus.

• Uncontrolled hypertension (systolic BP> 170 or diastolic BP> 100).

• Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening.