Nicotine Treatment of Cognitive Decline in Down Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Paul Newhouse, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01778946
First received: January 25, 2013
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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).

Condition Intervention Phase
Down Syndrome
Mild Cognitive Impairment
Drug: Low Dose Nicotine (7mg)
Drug: Moderate Dose Nicotine (14mg)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nicotinic Treatment of Age-Related Cognitive Decline in Down Syndrome: An Open Label Pilot Trial

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Safety [ Time Frame: 1 Month ] [ Designated as safety issue: Yes ]
    Measure safety of administering nicotine daily in terms of number and severity of adverse events.


Secondary Outcome Measures:
  • Cognitive Improvement [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
    Measure whether daily low-moderate dose transdermal nicotine can enhance cognitive function/performance (memory, learning, attention) in middle aged persons with Down Syndrome, identified as suffering from mild cognitive decline.

  • Exploratory [ Time Frame: 1 Month ] [ Designated as safety issue: No ]

    The investigators will measure daily low-moderate dose nicotine treatment's changes to

    1. electrophysiologic markers of cognitive status, and
    2. clinical, biological and cognitive effects of genes such as apolipoprotein E(APOE)/CYP2A6 and behavioral measures.


Estimated Enrollment: 15
Study Start Date: April 2013
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nicotine

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)
Other Names:
  • Transdermal Nicotine Patch
  • Nicotine Skin Patch
  • Adhesive Nicotine Patch
Drug: Moderate Dose Nicotine (14mg)
Other Names:
  • Transdermal Nicotine Patch
  • Nicotine Skin Patch
  • Adhesive Nicotine Patch

Detailed Description:

Over 50% of adults with Down Syndrome (DS) develop Alzheimer's disease (AD) by the age of 60 (Nadel 2003), and life expectancy in DS is now 50-60 years. Thus, age-associated cognitive impairment and dementia in older adults with DS is an urgent public health concern. The investigators propose that nicotinic stimulation is a promising strategy to stabilize or improve cognitive functioning in adults with DS, possibly with additional neuroprotective effects. The investigators have extensive experience investigating the role of nicotinic receptors on human cognition and impairment. This application takes advantage of new insights into treating Mild Cognitive Impairment (MCI-the precursor condition to Alzheimer's Disease (AD) in typically developing individuals) with nicotine to propose an open label pilot study of transdermal nicotine in middle-aged non-smoking DS patients who show early cognitive and/or behavioral changes consistent with MCI/dementia.

The goal of this study is to establish preliminary evidence for safety, gain preliminary evidence as to whether nicotine enhances cognitive functioning in DS adults, and examine electrophysiological, biological, and behavioral correlates of nicotinic stimulation effects.

The investigators propose that positive results on cognitive or functional indices that would lead to a larger and longer double-blind trial to test more definitively whether nicotinic stimulation may be cognitively and/or functionally enhancing for DS patients. The knowledge gained from the translational aspects of this project will guide the development of potentially 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. This work also represents the first time that cutting-edge advances in treating MCI/AD in the general population are immediately and rigorously applied to those with DS.

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778946

Contacts
Contact: Asante R Kamkwalala, B.S. 6153222082 asante.r.kamkwalala@vanderbilt.edu
Contact: Paul A Newhouse, M.D. 6159360928 paul.newhouse@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt Psychiatric Hospital Recruiting
Nashville, Tennessee, United States, 37212
Principal Investigator: Paul A Newhouse, MD         
Sub-Investigator: Elisabeth Dykens, PhD         
Sub-Investigator: Alexandra S Key, PhD         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Paul A Newhouse, MD Vanderbilt University Dept. of Psychiatry
Study Director: Asante R Kamkwalala, BS Vanderbilt Brain Institute-Neuroscience Graduate Program
  More Information

Additional Information:
No publications provided

Responsible Party: Paul Newhouse, Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01778946     History of Changes
Other Study ID Numbers: 121759
Study First Received: January 25, 2013
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Down Syndrome
Trisomy 21
Nicotine
Mild Cognitive Impairment
Event Related Potential
Memory
Attention
Neuroprotection
Cognitive Enhancement
Alzheimer's Disease
Dementia
APOE

Additional relevant MeSH terms:
Syndrome
Down Syndrome
Cognition Disorders
Mild Cognitive Impairment
Disease
Pathologic Processes
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014