Tourettes SyndromePhase 2NCT01172288

N-acetylcysteine (NAC) for Children With Tourette Syndrome

A Phase 2 study testing N-Acetylcysteine (NAC) in people with Tourettes Syndrome and Tic, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by multiple motor and vocal tics that last for at least a year in duration. Currently, there exist several effective pharmacological treatments for childhood tics including alpha-2 agonist medications (guanfacine and clonidine) and… Read more about this study

Who is it for?: Ages 8 to 17 years
Conditions the study is for: Tourettes Syndrome, Tic
What is being tested?: N-Acetylcysteine (NAC)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteUnited States
Study dates: Jul 2010to Jan 2014
Phase: Phase 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 8 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Children aged 8-17 years.
Primary diagnosis of Tourette syndrome or chronic tic disorder.
Duration of tics greater than 1 year.
Significant Current tic symptoms: Current YGTSS score greater than or equal to 22 with a TS diagnosis or greater than or equal to 14 with a chronic tic disorder.

Who cannot join

Comorbid bipolar disorder, psychotic disorder, substance use disorder, developmental disorder or mental retardation (IQ<70).
Recent change (less than 4 weeks) in medications that have potential effects on tic severity (such as neuroleptic medications, dopamine agonists, alpha-2 agonists (guanfacine, clonidine or prazosin), SSRIs, clomipramine, naltrexone, lithium, psychostimulants, or anxiolytics). Medication change is defined to include dose changes or medication discontinuation.
Recent change in behavioral treatment for Tourette syndrome or comorbid conditions (i.e. OCD) within the last 4 weeks or initiation of behavioral therapy for tics within the last 12 weeks.
Asthma requiring medication use within the last 3 months
Known hypersensitivity or previous anaphylactoid reaction to acetylcysteine or any components in its preparation
Positive pregnancy test or drug screening test.
Previous use of N-acetylcysteine (dose greater than 600mg for more than 2 weeks)

Trial locations and contacts

1 site in 1 country.

United States1 site

Yale Child Study Center
New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Children With Tourette Syndrome

N-acetylcysteine (NAC) is a natural supplement that acts as an antioxidant and glutamate modulating agent. NAC has been used safely for decades in doses 20-40 times higher than in this trial as an antidote for acetaminophen overdose. The only side-effect commonly seen with NAC is nausea and this side-effect is seldom seen in the doses used in this trial.

NAC has recently been demonstrated to be effective in a double-blind, placebo-controlled trial in adults with trichotillomania (chronic hair pulling). Hairpulling is hypothesized to be closely related to tics because these conditions (1) have similar clinical characteristics -- both groups typically experience urges before engaging in pulling or tics, (2) neuroimaging studies suggest they involve similar brain circuits -- the basal ganglia, (3) the same pharmacological treatments (neuroleptics) may be effective for both conditions and (4) they tend to be inherited together in families. In other trials NAC has evidence of some efficacy in treating diverse psychiatric conditions such as bipolar depression, schizophrenia and cocaine dependence.

The investigators are conducting this trial to determine if NAC is an effective treatment for tics.

Conditions: Tourettes Syndrome, Tic
Being tested: N-Acetylcysteine (NAC), Placebo
Keywords: Tic disorders,, Tourette syndrome, Chronic Tic Disorders
Medical subject headings: Tourette Syndrome, Tics, Tic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-Acetylcysteine (NAC)Drug
1 600mg capsule twice a day for 2 weeks and then 2 600mg capsules twice a day for the remaining 10 weeks of the trial.
PlaceboDrug
1 600mg Capsule twice a day for two weeks then 2 600mg capsules twice a day for the remaining 10 weeks of the study. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.

Study groups in NCT01172288
Study group	Role	What they receive
N-Acetylcysteine	Experimental	NAC was titrated up to a maximum dose of 2400 mg over the course of 2 weeks. Subjects were assigned 600 mg twice a day for weeks 1-2, and then were assigned 1200 mg twice a day for the remainder of the 12 week study. Receives: Drug: N-Acetylcysteine (NAC)
Placebo	Placebo comparator	Placebo: Subjects were assigned to take two capsules twice a day for weeks 1-2, and then were assigned 4 capsules twice a day for the remainder of the 12 week study. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Improvement in Tic Severity
Yale Global Tic Severity Scale is a standard psychiatric measure that rates tics from 0 (no tics) to 100 (most severe tics).
It separately rates motor tics and vocal tics in 5 subscales (number, frequency, intensity, complexity and interference) where the maximum severity score for motor tics is 25 and for vocal tics is 25. Giving us the Total Tic Severity Score maximum of 50.
The additional Impairment Scale rates the degree of disability caused by the tics ranging from 0 (none) to 50 (severe). When these two scores are added we get the Yale Global Tic Severity Scale Score.
Measured: 12 weeks

Secondary outcomes (4)

Improvement of Premonitory Urges
Premonitory Urge for Tics Scale (PUTS). Items are rated on a scale of 1-4 from "least" to "most." A total score is calculated by summing the scores of all items. Nine is the minimum possible score. A score of 12.5-24.5 indicates medium intensity of premonitory urges for tics. A score of 25-30.5 indicates high intensity which may be associated with marked impairment. Scores 31 and above indicate extremely high intensity with probable severe impairment. A score of 36 is the maximum score possible.
Measured: 12 weeks
Improvement in OCD Severity
Childrens' Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). 10-item scale. Each item is rated from 0-4. A sum total is calculated by adding items 1-10. 0-7: Subclinical. 8-15: Mild. 16-23: Moderate. 24-31: Severe. 32-40: Extreme.
Measured: 12 weeks
Overall Improvement
Clinical Global Impression - Improvement Scale (CGI-I). The CGI is a 7-point scare that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.
Measured: 12 weeks
Number of Participants With Adverse Effects
Number of participants with adverse events according to the Pediatric Adverse Events Rating Scale
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2010Jan 2014

First posted29 Jul 2010 (estimated)
Study startJul 2010
Primary completionJan 2014
Study completionJan 2014

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 (7)Papers the sponsor has linked to this study.
Other trials for Tourettes SyndromeStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01172288
Sponsor's protocol ID: YCSC1004006637
Status last verified: Dec 2016
First submitted: 27 Jul 2010
Last updated: 10 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009 Jul;66(7):756-63. doi: 10.1001/archgenpsychiatry.2009.60.
PubMed 19581567
Bloch MH, Leckman JF. Clinical course of Tourette syndrome. J Psychosom Res. 2009 Dec;67(6):497-501. doi: 10.1016/j.jpsychores.2009.09.002.
PubMed 19913654
Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI. N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008 Sep 15;64(6):468-75. doi: 10.1016/j.biopsych.2008.04.022. Epub 2008 Jun 5.
PubMed 18534556
Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
PubMed 18436195
Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008 Sep;11(6):851-76. doi: 10.1017/S1461145707008401. Epub 2008 Jan 21.
PubMed 18205981
Singer HS, Morris C, Grados M. Glutamatergic modulatory therapy for Tourette syndrome. Med Hypotheses. 2010 May;74(5):862-7. doi: 10.1016/j.mehy.2009.11.028. Epub 2009 Dec 21.
PubMed 20022434
Bloch MH, Panza KE, Yaffa A, Alvarenga PG, Jakubovski E, Mulqueen JM, Landeros-Weisenberger A, Leckman JF. N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial. J Child Adolesc Psychopharmacol. 2016 May;26(4):327-34. doi: 10.1089/cap.2015.0109. Epub 2016 Mar 30.
PubMed 27027204

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Tourettes Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Children With Tourette Syndrome
ClinicalTrials.gov ID: NCT01172288
Acronym / sponsor ID: YCSC1004006637
Conditions: Tourettes Syndrome, Tic
Keywords: Tic disorders,, Tourette syndrome, Chronic Tic Disorders
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: American Academy of Child Adolescent Psychiatry.
Study start: Jul 2010
Primary completion: Jan 2014 (actual)
Study completion: Jan 2014 (actual)
First posted: 29 Jul 2010 (estimated)
Results: Posted 19 Dec 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The investigators are conducting this trial to determine if NAC is an effective treatment for tics.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
N-Acetylcysteine	Experimental	Drug: N-Acetylcysteine (NAC)NAC was titrated up to a maximum dose of 2400 mg over the course of 2 weeks. Subjects were assigned 600 mg twice a day for weeks 1-2, and then were assigned 1200 mg twice a day for the remainder of the 12 week study.
Placebo	Placebo comparator	Drug: PlaceboPlacebo: Subjects were assigned to take two capsules twice a day for weeks 1-2, and then were assigned 4 capsules twice a day for the remainder of the 12 week study.

Who may qualify

Ages: 8 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

Children aged 8-17 years.
Primary diagnosis of Tourette syndrome or chronic tic disorder.
Duration of tics greater than 1 year.
Significant Current tic symptoms: Current YGTSS score greater than or equal to 22 with a TS diagnosis or greater than or equal to 14 with a chronic tic disorder.

Key exclusion criteria (7 listed)

Comorbid bipolar disorder, psychotic disorder, substance use disorder, developmental disorder or mental retardation (IQ<70).
Recent change (less than 4 weeks) in medications that have potential effects on tic severity (such as neuroleptic medications, dopamine agonists, alpha-2 agonists (guanfacine, clonidine or prazosin), SSRIs, clomipramine, naltrexone, lithium, psychostimulants, or anxiolytics). Medication change is defined to include dose changes or medication discontinuation.
Recent change in behavioral treatment for Tourette syndrome or comorbid conditions (i.e. OCD) within the last 4 weeks or initiation of behavioral therapy for tics within the last 12 weeks.
Asthma requiring medication use within the last 3 months
Known hypersensitivity or previous anaphylactoid reaction to acetylcysteine or any components in its preparation

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
N-Acetylcysteine (NAC)1 600mg capsule twice a day for 2 weeks and then 2 600mg capsules twice a day for the remaining 10 weeks of the trial.	Drug	N-Acetylcysteine
Placebo1 600mg Capsule twice a day for two weeks then 2 600mg capsules twice a day for the remaining 10 weeks of the study. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.	Drug	Placebo

Primary outcome

Improvement in Tic Severity
Time frame: 12 weeks
Yale Global Tic Severity Scale is a standard psychiatric measure that rates tics from 0 (no tics) to 100 (most severe tics). It separately rates motor tics and vocal tics in 5 subscales (number, frequency, intensity, complexity and interference) where the maximum severity score for motor tics is 25 and for vocal tics is 25. Giving us the Total Tic Severity Score maximum of 50. The additional Impairment Scale rates the degree of disability caused by the tics ranging from 0 (none) to 50 (severe). When these two scores are added we get the Yale Global Tic Severity Scale Score.

4 secondary outcomes

Improvement of Premonitory Urges
Time frame: 12 weeks
Improvement in OCD Severity
Time frame: 12 weeks
Overall Improvement
Time frame: 12 weeks
Number of Participants With Adverse Effects
Time frame: 12 weeks

Results and safety

Results posted to the registry on 19 Dec 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
N-Acetylcysteine	17	16
Placebo	14	13

Primary outcome: Improvement in Tic Severity

Time frame: 12 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	N-Acetylcysteine n = 17	Placebo n = 14
Value	24.3 (7.9)	21.3 (4.6)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Every 4 weeks until the completion of the 12-week study. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
N-Acetylcysteine	0 of 17 (0%)	2 of 17 (11.8%)	Not reported
Placebo	0 of 14 (0%)	7 of 14 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19581567Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009 Jul;66(7):756-63. doi: 10.1001/archgenpsychiatry.2009.60.
Background: PubMed 19913654Bloch MH, Leckman JF. Clinical course of Tourette syndrome. J Psychosom Res. 2009 Dec;67(6):497-501. doi: 10.1016/j.jpsychores.2009.09.002.
Background: PubMed 18534556Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI. N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008 Sep 15;64(6):468-75. doi: 10.1016/j.biopsych.2008.04.022. Epub 2008 Jun 5.
Background: PubMed 18436195Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
Background: PubMed 18205981Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008 Sep;11(6):851-76. doi: 10.1017/S1461145707008401. Epub 2008 Jan 21.
Background: PubMed 20022434Singer HS, Morris C, Grados M. Glutamatergic modulatory therapy for Tourette syndrome. Med Hypotheses. 2010 May;74(5):862-7. doi: 10.1016/j.mehy.2009.11.028. Epub 2009 Dec 21.
Results publication: PubMed 27027204Bloch MH, Panza KE, Yaffa A, Alvarenga PG, Jakubovski E, Mulqueen JM, Landeros-Weisenberger A, Leckman JF. N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial. J Child Adolesc Psychopharmacol. 2016 May;26(4):327-34. doi: 10.1089/cap.2015.0109. Epub 2016 Mar 30.
Yale Child Study Center TS/OCD ClinicLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Tourettes Syndrome

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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.

Michael H. Bloch, MD, MS principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-Acetylcysteine (NAC) in people with Tourettes Syndrome and Tic, 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 4 inclusion and 7 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 Feb 2017. 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. Some participants in this study may receive a placebo. 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 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 19 Dec 2016). 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?

Improvement in Tic Severity (time frame: 12 weeks). 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 NCT01172288, which also lists 7 linked publications.

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 Feb 2017.