N-acetylcysteine (NAC) for Pediatric Obsessive-Compulsive Disorder

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01172275
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 67.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Pediatric Obsessive-Compulsive Disorder (OCD) affects 1-3% of children. The investigators currently have effective first-line interventions for pediatric OCD such as Cognitive Behavioral Therapy (CBT) and pharmacotherapy with serotonin reuptake inhibitors (SRIs). However, roughly half of children with OCD still have clinically significant OCD symptoms despite treatment with first-line pharmacological treatments and CBT interventions for OCD. Furthermore, all pharmacological treatments for OCD in children have an increased side effect burden when compared to adults. Novel treatments for children with OCD are needed.

N-acetylcysteine (NAC) is a natural supplement that acts as an antioxidant and a 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). Trichotillomania is an obsessive-compulsive spectrum disorder that is hypothesized to be closely related to OCD. 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 effective in treating OCD.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder	Drug: N-Acetylcysteine; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-Blind, Placebo-Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Pediatric Obsessive-Compulsive Disorder
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Feb 13, 2017
• Actual Study Completion Date: Feb 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N-Acetylcysteine N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.	Drug: N-Acetylcysteine; 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.; Other Names: PharmaNAC
Placebo Comparator: Placebo Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.	Other: Placebo; 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.

Outcome Measures

Primary Outcome Measures

1. OCD Severity at 12 Weeks [12 weeks]

   Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) (0-7:Subclinical, 8-15: Mild, 16-23: Moderate, 24-31: Severe, 32-40: Extreme)

Secondary Outcome Measures

1. Overall Improvement at 12 Weeks [12 weeks]

   Clinician Global Improvement Scale (CGI) 0=Not assessed 4=Moderately ill Normal, not at all ill 5=Markedly ill Borderline mentally ill 6=Severly ill Mildly ill 7=Very much worse

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Children aged 8-17 years.

• Primary diagnosis of OCD.

• Duration of OCD greater than 6 months.

• Significant Current OCD symptoms: Current CY-BOCS score > or = 16.

Exclusion Criteria:

• 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 OCD severity (such as Selective Serotonin Reuptake Inhibitors, clomipramine, naltrexone, lithium, psychostimulants, anxiolytics, or antipsychotics). Medication change is defined to include either dose changes or medication discontinuation.

• Recent change in behavioral treatment for OCD or comorbid conditions 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 (case reports have linked intravenous NAC administration with asthma exacerbation)

• 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).

• Previous history or suspicion of cystinuria because of a possibility of forming kidney stones.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Child Study Center	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Michael H. Bloch, MD, MS, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 17, 2017

More Information

Additional Information:

• Yale Child Study Center TS/OCD Clinic
• Yale OCD Adult Research Clinic

Publications

• 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.
• 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.
• 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.
• Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, Sanacora G, Krystal JH, Coric V. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology (Berl). 2006 Jan;184(2):254-6. Epub 2005 Dec 22.
• 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. Review.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01172275
• Other Study ID Numbers: 1004006623
• First Posted: Jul 29, 2010
• Last Update Posted: Sep 6, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Yale University: Obsessive-Compulsive Disorder; OCD
• Additional relevant MeSH terms: Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. N-Acetylcysteine: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.	Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial. Placebo: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.
Period Title: Overall Study
STARTED	5	6
COMPLETED	3	6
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	N-Acetylcysteine	Placebo	Total
Arm/Group Description	N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. N-Acetylcysteine: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.	Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial. Placebo: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.	Total of all reporting groups
Overall Participants	5	6	11
Age (Count of Participants)
<=18 years	5 100%	6 100%	11 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 60%	5 83.3%	8 72.7%
Male	2 40%	1 16.7%	3 27.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	6 100%	11 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	6 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	OCD Severity at 12 Weeks
Description	Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) (0-7:Subclinical, 8-15: Mild, 16-23: Moderate, 24-31: Severe, 32-40: Extreme)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. N-Acetylcysteine: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.	Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial. Placebo: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.
Measure Participants	5	6
Mean (Standard Deviation) [points on a scale]	21.4 (4.65)	21.3 (4.64)

2. Secondary Outcome

Title	Overall Improvement at 12 Weeks
Description	Clinician Global Improvement Scale (CGI) 0=Not assessed 4=Moderately ill Normal, not at all ill 5=Markedly ill Borderline mentally ill 6=Severly ill Mildly ill 7=Very much worse
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. N-Acetylcysteine: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.	Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial. Placebo: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.
Measure Participants	5	6
Mean (Standard Deviation) [score on a scale]	3.2 (1.16)	3.5 (0.90)

Adverse Events

Time Frame	Adverse events were collected up until 12 weeks.
Arm/Group Title	N-Acetylcysteine		Placebo
Arm/Group Description	N-Acetylcysteine effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. N-Acetylcysteine: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial.		Placebo effervescent tablets. 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial. Placebo: 1 900mg tablet once a day for 1 week, then 1 900mg tablet twice a day for 1 week and then 1 900mg tablet three times a day for the remaining 10 weeks of the trial. Children receiving placebo will be offered the active intervention after the double-blind portion of the trial.
All Cause Mortality
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)
Serious Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/6 (16.7%)
Gastrointestinal disorders
Diarrhea	0/5 (0%)	0	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Skin Rash	1/5 (20%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.