Nicotine Treatment of Cognitive Decline in Down Syndrome

NCT01778946 | Completed Phase 1 Results

• 1 other identifier: 121759
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Down Syndrome; Mild Cognitive Impairment

Keywords

Nicotine; Down Syndrome; Mild Cognitive Impairment; Event Related Potential; Memory; Attention; Trisomy 21; Neuroprotection; Cognitive Enhancement; Alzheimer's Disease; Dementia; APOE

Outcome Measures

Primary Outcomes (1)

• Tolerability of Nicotine Intervention

  Maximum transdermal nicotine dosage able to be maintained stably by participants.

  1 Month

Secondary Outcomes (5)

• Cognitive Improvement - Simple Response Time

  4 time-points over the 6-week testing period: at baseline, day 14, day 28 (end of treatment), and 2-weeks post-treatment on day 42.

• Exploratory - Event-Related Potentials

  4 time-points over the 6-week testing period: at baseline, day 14, day 28 (end of treatment), and 2-weeks post-treatment on day 42.

• Cognitive Improvement - Continuous Performance Test

  4 time-points over the 6-week testing period: at baseline, day 14, day 28 (end of treatment), and 2-weeks post-treatment on day 42.

• Cognitive Improvement - Buschke Selective Reminding Task

  4 time-points over the 6-week testing period: at baseline, day 14, day 28 (end of treatment), and 2-weeks post-treatment on day 42.

• Cognitive Improvement - Critical Flicker Fusion Task

  4 time-points over the 6-week testing period: at baseline, day 14, day 28 (end of treatment), and 2-weeks post-treatment on day 42.

Study Arms (1)

Nicotine

EXPERIMENTAL

Low Dose Nicotine (7mg) Moderate Dose Nicotine (14mg) All participants in study will begin with the 7mg patch, titrating from 2 hours/day to a full 16 hours/day over the course of the first 7 days (based on individual tolerance). Day 7 - Day 28 of the study, participants will apply a new nicotine patch daily. Depending on tolerance, some participants may increase to the moderate dose (14mg) patch. All participants will apply a new patch daily for a total of 28 days (1 month)

Drug: Low Dose Nicotine (7mg); Drug: Moderate Dose Nicotine (14mg)

Interventions

Low Dose Nicotine (7mg) DRUG

Also known as: Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch

Nicotine

Moderate Dose Nicotine (14mg) DRUG

Also known as: Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch

Nicotine

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

Related Links

• Website for the Vanderbilt Center for Cognitive Medicine
• Website for the Vanderbilt Kennedy Center for research concerning developmental disabilities
• Website for the Down Syndrome Association of Middle Tennessee

MeSH Terms

Conditions

Down Syndrome; Cognitive Dysfunction; Alzheimer Disease; Dementia

Interventions

Nicotine; Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Therapeutics

Results Point of Contact

• Title: Dr. Paul Newhouse
• Organization: Vanderbilt University Medical Center

paul.newhouse@vanderbilt.edu

6159360928

Study Officials

• Paul A Newhouse, MD

  Vanderbilt University Dept. of Psychiatry

  PRINCIPAL INVESTIGATOR

• Alexander C Conley, PhD

  Vanderbilt University Medical Center Dept. of Psychiatry

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 29, 2013
• Study Start: April 1, 2013
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: May 10, 2022
• Results First Posted: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)