Down SyndromePhase 1/2NCT01778946
Nicotine Treatment of Cognitive Decline in Down Syndrome
A Phase 1/2 study testing Low Dose Nicotine (7mg) and Moderate Dose Nicotine (14mg) in people with Down Syndrome and Mild Cognitive Impairment, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Down Syndrome, Mild Cognitive Impairment
- What is being tested?
- Low Dose Nicotine (7mg) and Moderate Dose Nicotine (14mg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Feb 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 16Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Psychiatric Hospital
Nashville, Tennessee, 37212
About this study
Official title: Nicotinic Treatment of Age-Related Cognitive Decline in Down Syndrome: An Open Label Pilot Trial
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).
Read the 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.
- Conditions
- Down Syndrome, Mild Cognitive Impairment
- Being tested
- Low Dose Nicotine (7mg), Moderate Dose Nicotine (14mg)
- Keywords
- Nicotine, Down Syndrome, Mild Cognitive Impairment, Event Related Potential, Memory, Attention, Trisomy 21, Neuroprotection, Cognitive Enhancement, Alzheimer's Disease, Dementia, APOE
- Medical subject headings
- Down Syndrome, Cognitive Dysfunction, Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose Nicotine (7mg)Drug
Also called Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch
Moderate Dose Nicotine (14mg)Drug
Also called Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Low Dose Nicotine (7mg); Drug: Moderate Dose Nicotine (14mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of Nicotine Intervention
Maximum transdermal nicotine dosage able to be maintained stably by participants.
Measured: 1 Month
Secondary outcomes (5)
Cognitive Improvement - Simple Response Time
Psychomotor speed was measured by the performance on the CANTAB simple reaction time task
Measured: 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
The investigators will measure daily low-moderate dose nicotine treatment's changes to electrophysiological markers of memory performance using an incidental memory task. The incidental memory task consists of presenting participants with a series of 60 complex images, 50 of which are presented once, and 10 which are repeated 5 times each. The task measures the presence of the late positive potential (LPP), a positive deflection over the parietal cortex which is elevated for the repeated compared to the singly presented images. The presence of this potential is indicative of improved recognition memory.
Measured: 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
Performance on the Conners' Continuous Performance Test, which is a measure of sustained attention. The main outcome measure was commission errors, which measures attention failures. The commission errors are calculated as T-scores. Higher T-scores indicate worse performance, lower T-scores indicate better performance. Average performance is a score of 50, with a standard deviation of 10.
Measured: 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
Episodic memory performance was assessed by the Buschke Selective Reminding Task. The main outcome metric of this test was the total words correctly recalled.
Measured: 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
Arousal and vigilance were measured by the Critical Flicker Fusion task. The task used at perceptual performance on ascending and descending frequencies of the task.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startApr 2013
- Primary completionFeb 2021
- Study completionFeb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Newhouse, Vanderbilt University Medical Center
- Investigators
- Paul A Newhouse, MD, Principal investigator, Vanderbilt University Dept. of PsychiatryAlexander C Conley, PhD, Study director, Vanderbilt University Medical Center Dept. of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01778946
- Sponsor's protocol ID
- 121759
- Status last verified
- May 2022
- First submitted
- 25 Jan 2013
- Last updated
- 10 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nicotinic Treatment of Age-Related Cognitive Decline in Down Syndrome: An Open Label Pilot Trial
- ClinicalTrials.gov ID
- NCT01778946
- Acronym / sponsor ID
- 121759
- Conditions
- Down Syndrome, Mild Cognitive Impairment
- Keywords
- Nicotine, Down Syndrome, Mild Cognitive Impairment, Event Related Potential, Memory, Attention, Trisomy 21, Neuroprotection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Feb 2021 (actual)
- Study completion
- Feb 2021 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Posted 10 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nicotine | Experimental | Drug: Low Dose Nicotine (7mg), Drug: Moderate Dose Nicotine (14mg)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) |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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+.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose Nicotine (7mg)Also: Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch | Drug | Nicotine |
| Moderate Dose Nicotine (14mg)Also: Transdermal Nicotine Patch, Nicotine Skin Patch, Adhesive Nicotine Patch | Drug | Nicotine |
Primary outcome
Tolerability of Nicotine Intervention
Time frame: 1 Month
Maximum transdermal nicotine dosage able to be maintained stably by participants.
5 secondary outcomes
Cognitive Improvement - Simple Response Time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Website for the Vanderbilt Center for Cognitive MedicineLink provided by the sponsor.
- Website for the Vanderbilt Kennedy Center for research concerning developmental disabilitiesLink provided by the sponsor.
- Website for the Down Syndrome Association of Middle TennesseeLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Down Syndrome
Not yet recruitingPhase 4
Oral Switch in Bloodstream Infections in Immunocompromised Children
Bloodstream Infection, Bloodstream Infection Due to Central Venous Catheter
Not yet recruiting
Fecal Microbiota Transplantation (FMT) to Slow Biological Aging
Aging, Healthy, Aging and Cognitive Health
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul A Newhouse, MD principal investigator
Vanderbilt University Dept. of Psychiatry
Alexander C Conley, PhD study director
Vanderbilt University Medical Center Dept. of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low Dose Nicotine (7mg) and Moderate Dose Nicotine (14mg) in people with Down Syndrome and Mild Cognitive Impairment, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability of Nicotine Intervention (time frame: 1 Month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.