Autism Spectrum DisorderPhase 1NCT02552147
Nicotinic Cholinergic Modulation as a Novel Treatment Strategy for Aggression Associated With Autism
A Phase 1 study testing Transdermal nicotine in people with Autism Spectrum Disorder and Aggression, run by Yale University at 1 site in United States.
Trial summary
Some individuals with autism spectrum disorders (ASD) also demonstrate irritability or aggression, which can interfere with functioning. The purpose of this pilot study is to test whether transdermal nicotine is effective for irritability and/or aggression in adults with ASD using a double-blind, placebo-controlled… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Autism Spectrum Disorder, Aggression, Irritability
- What is being tested?
- Transdermal nicotine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to 17 Nov 2017
- Phase
- Phase 1
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age: 18-60
- Gender: All
- Language: Communicative in English
- Participants with a prior diagnosis of DSM-5 ASD at some point in their lifetime OR a DSM-4 diagnosis of Autism OR a DSM-4 diagnosis of Asperger's syndrome OR a DSM-4 diagnosis of Pervasive Developmental Disorder Not Otherwise Specified.
- Symptoms of irritability, agitation or aggression as reported by parent and/or participant
- Aberrant behavior checklist - Irritability Subscale (ABC-I) score of 16 or higher
Show all 9Show fewer
- No changes in psychotropic medications within the past 14 days.
- Either lives with a primary caregiver or closely engaged with a primary caregiver who interacts with the patient daily
- BMI > 17.5 and < 45
Who cannot join
- Age < 18 or > 60
- BMI < 17.5 or > 45
- Currently using tobacco or any nicotine products (transdermal, gum, e-cigarettes)
- Changes in psychotropic medication management within the past 14 days
- Previous allergy to transdermal patches
- Patients with heart rate > 100 or < 50 or known history of cardiac rhythm abnormalities
Show all 10Show fewer
- Systolic blood pressure > 150 or < 95; diastolic blood pressure > 90 or < 50
- No symptoms of irritability, agitation, or aggression as reported by parent and/or participant
- ABC-I score of less than 16
- No primary caregiver, or primary caregiver unable to assist with rating scales
Trial locations and contacts
1 site in 1 country.
About this study
Some individuals with autism spectrum disorders (ASD) also demonstrate irritability or aggression, which can interfere with functioning. The purpose of this pilot study is to test whether transdermal nicotine is effective for irritability and/or aggression in adults with ASD using a double-blind, placebo-controlled clinical trial. Subjects will participate in three visits. At the first visit, subjects are screened for eligibility and enrolled. Baseline measures include rating scales and a frustrative computerized task. They will then wear seven days of transdermal nicotine or placebo. Visit two is on day seven and the study measures are repeated, vital signs and side effects monitored. Subjects will return for a third and final visit on day 21 to repeat the study measures performed during visit two.
- Conditions
- Autism Spectrum Disorder, Aggression, Irritability
- Being tested
- Transdermal nicotine, Transdermal placebo
- Keywords
- Autism spectrum disorder, Aggression, Irritability, Nicotine, Nicotinic acetylcholine receptor, Nicotinic agonist, Adult autism
- Medical subject headings
- Autism Spectrum Disorder, Aggression, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal nicotineDrug
Transdermal placeboOther
| Study group | Role | What they receive |
|---|---|---|
| Transdermal nicotine first, placebo last | Experimental | Subject will receive transdermal nicotine 7 mg daily for 7 days, placebo patch for 7 days, then placebo patch for a final 7 days. Receives: Drug: Transdermal nicotine; Other: Transdermal placebo |
| Transdermal placebo first, nicotine last | Experimental | Subject will receive transdermal placebo daily for 7 days, placebo patch for another 7 days, then transdermal nicotine 7 mg daily for a final 7 days. Receives: Drug: Transdermal nicotine; Other: Transdermal placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I)
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-irritability subscale measures irritability and related symptoms and the subscale score range is 0 (least symptomatic) to 45 (most symptomatic). The ABC is completed by parents/caregivers.
Measured: Baseline and 7 days.
Secondary outcomes (5)
Change in Social Responsiveness Scale-Adults (SRS-A)
The Social Responsiveness Scale (SRS) - 2 quantifies impairments in social behaviors seen in autism spectrum disorder and related conditions and their severity. The version used in this study is completed by parents/caregivers. The raw score range is 0 (unaffected) to > 134 (extremely affected). The ABC is completed by parents/caregivers.
Measured: Baseline and 7 days.
Change in Qualitative Description of Irritability and Aggression Symptoms
Brief qualitative reports of the patient's subjective experience will be recorded by asking "In what ways did you find the patch helpful or harmful during the past week, if at all?".
Measured: Baseline and 7 days
Change in Frustration and Irritability Ratings During Frustration-induction Go-NoGo Task
Subjects will perform a computerized frustration-induction task and complete a rating scale of irritability and frustration levels.
Measured: Baseline and one week
Change in State/Trait Anxiety Inventory (STAI) Score
The State-Trait Anxiety Inventory (STAI) is a measure of trait and state anxiety. It ranges from a score of 20 (least affected) to 80 (most affected).
Measured: Baseline and day 7
Nightly Sleep Quality
Caregivers rated nightly sleep quality from 0 (worst) to 10 (best). Average rating for each treatment week is compared.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2015 (estimated)
- Study startSep 2015
- Primary completion17 Nov 2017
- Study completion17 Nov 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Autism Speaks
- Responsible party
- Sponsor
- Investigators
- Alan S Lewis, MD, PhD, Principal investigator, Lecturer in psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02552147
- Sponsor's protocol ID
- 1502015384
- Status last verified
- May 2022
- First submitted
- 14 Sep 2015
- Last updated
- 6 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nicotinic Cholinergic Modulation as a Novel Treatment Strategy for Aggression Associated With Autism
- ClinicalTrials.gov ID
- NCT02552147
- Acronym / sponsor ID
- 1502015384
- Conditions
- Autism Spectrum Disorder, Aggression, Irritability
- Keywords
- Autism spectrum disorder, Aggression, Irritability, Nicotine, Nicotinic acetylcholine receptor, Nicotinic agonist, Adult autism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Autism Speaks
- Study start
- Sep 2015
- Primary completion
- 17 Nov 2017 (actual)
- Study completion
- 17 Nov 2017 (actual)
- First posted
- 16 Sep 2015 (estimated)
- Results
- Posted 14 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some individuals with autism spectrum disorders (ASD) also demonstrate irritability or aggression, which can interfere with functioning. The purpose of this pilot study is to test whether transdermal nicotine is effective for irritability and/or aggression in adults with ASD using a double-blind, placebo-controlled clinical trial. Subjects will participate in three visits. At the first visit, subjects are screened for eligibility and enrolled. Baseline measures include rating scales and a frustrative computerized task. They will then wear seven days of transdermal nicotine or placebo. Visit two is on day seven and the study measures are repeated, vital signs and side effects monitored. Subjects will return for a third and final visit on day 21 to repeat the study measures performed during visit two.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transdermal nicotine first, placebo last | Experimental | Drug: Transdermal nicotine, Other: Transdermal placeboSubject will receive transdermal nicotine 7 mg daily for 7 days, placebo patch for 7 days, then placebo patch for a final 7 days. |
| Transdermal placebo first, nicotine last | Experimental | Drug: Transdermal nicotine, Other: Transdermal placeboSubject will receive transdermal placebo daily for 7 days, placebo patch for another 7 days, then transdermal nicotine 7 mg daily for a final 7 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age: 18-60
- Gender: All
- Language: Communicative in English
- Participants with a prior diagnosis of DSM-5 ASD at some point in their lifetime OR a DSM-4 diagnosis of Autism OR a DSM-4 diagnosis of Asperger's syndrome OR a DSM-4 diagnosis of Pervasive Developmental Disorder Not Otherwise Specified.
- Symptoms of irritability, agitation or aggression as reported by parent and/or participant
Key exclusion criteria (10 listed)
- Age < 18 or > 60
- BMI < 17.5 or > 45
- Currently using tobacco or any nicotine products (transdermal, gum, e-cigarettes)
- Changes in psychotropic medication management within the past 14 days
- Previous allergy to transdermal patches
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 |
|---|---|---|
| Transdermal nicotine | Drug | Transdermal nicotine first, placebo last, Transdermal placebo first, nicotine last |
| Transdermal placebo | Other | Transdermal nicotine first, placebo last, Transdermal placebo first, nicotine last |
Primary outcome
Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I)
Time frame: Baseline and 7 days.
Aberrant Behavior Checklist (ABC) measures symptom subscales for individuals with neurodevelopmental disorders. The ABC-irritability subscale measures irritability and related symptoms and the subscale score range is 0 (least symptomatic) to 45 (most symptomatic). The ABC is completed by parents/caregivers.
5 secondary outcomes
Change in Social Responsiveness Scale-Adults (SRS-A)
Time frame: Baseline and 7 days.
Change in Qualitative Description of Irritability and Aggression Symptoms
Time frame: Baseline and 7 days
Change in Frustration and Irritability Ratings During Frustration-induction Go-NoGo Task
Time frame: Baseline and one week
Change in State/Trait Anxiety Inventory (STAI) Score
Time frame: Baseline and day 7
Nightly Sleep Quality
Time frame: Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
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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.
Alan S Lewis, MD, PhD principal investigator
Lecturer in 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 study testing Transdermal nicotine in people with Autism Spectrum Disorder and Aggression, run by Yale University 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 9 inclusion and 10 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 6 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 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.
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 14 Mar 2019). 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?
Change From Baseline in Aberrant Behavior Checklist Irritability Subscale (ABC-I) (time frame: Baseline and 7 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02552147, which also lists 1 linked publication.
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 6 May 2022; AzTrials last refreshed its copy on 31 Oct 2026.