Open Label Trial of Aripiprazole in Children and Adolescents With Tourette's Disorder

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00241176
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 53
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if Abilify will reduce tics (repetitive, uncontrollable movements or vocalizations) in children and adolescents ages 7-18 with Tourette's Disorder (TD) or a chronic motor tic disorder (either repetitive, uncontrollable movements or vocalizations).

Condition or Disease	Intervention/Treatment	Phase
Tourette's Syndrome; Tic Disorders	Drug: Aripiprazole	Phase 4

Detailed Description

The aims of this study are to obtain systematic data regarding dosing and safety of aripiprazole (Abilify) in the treatment of youth with Tourette's Disorder (TD). Tourette's Disorder is characterized by multiple motor (more than one uncontrollable movement) and vocal tics (vocal outbursts) which have been present for more than 1 year, with onset before the age of 18. The disorder causes marked distress in social, occupational or other important areas of functioning. Abilify has been approved by the United States Food and Drug Administration (FDA) to treat adults with schizophrenia but has not been approved to treat Tourette's Disorder (TD) so it is considered experimental or investigational in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Trial of Aripiprazole in Children and Adolescents With Tourette's Disorder
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Aripiprazole

Drug: Aripiprazole; Baseline Visit 2: Subjects btw 25-50kg start on 1.25mg/day, btw 50-70kg start on 2.5mg/day, greater than 70kg start on 5mg/day Visit 3: Titrated based on YGTSS & CGI-TS ratings at investigator discretion. Subjects who show evidence of response (reduction in CGI-TS by 1-2 points) may remain on same dose. Subjects who show no response may increase as follows: btw 25-50kg increase to 2.5mg/day, btw 50-70kg increase to 3.75mg/day, greater than 70kg increase to 7.5mg/day Visit 5: Subjects who show no response may increase as follows: btw 25-50kg increase to 3.75mg/day, btw 50-70kg increase to 5mg/day, greater than 70kg increase to 10mg/day Visit 6: Subjects who show no response may be increase as follows: btw 25-50kg increase to 5mg/day, btw 50-70kg increase to 7.5mg/day, greater than 70kg increase to 12.5mg/day Visit 7: Subjects who how no response may be increase as follows: btw 25-50kg increase to 7.5mg/day, btw 50-70kg increase to 10mg/day, greater than 70kg increase to 15mg/day

Outcome Measures

Primary Outcome Measures

1. Calculating Difference Between Means (Baseline and Endpoint Scores on the Yale Global Tic Severity Scale Subscales) [8 Weeks]

   The Yale Global Tic Severity Scale (YGTSS) is a clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The maximum YGTSS Global score is 100, while the maximum motor score is 25, the maximum vocal score is 25, and the maximum impairment score is 50. Higher scores indicate more severe tics.

Secondary Outcome Measures

1. Clinical Global Impression Severity Scores [24 Months]

   The Clinical Global Impression scale (CGI) is a classic instrument for making global assessments. This scale yields three different measures: 1. Severity of illness (7-point scale, with 7 being the most impaired; assessment of patient's current symptom severity, referred to here as CGIs), 2. Global improvement (7-point scale, with 7 being the most impaired; comparison of patient's baseline condition with his/her current condition, referred to here as CGIi), 3. Efficacy index (4 point x 4 point rating scale, comparison of patient's baseline condition with a ratio of current therapeutic benefit to severity of side effects)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Child or adolescent must be 7 to 18 years of age (inclusive) when informed consent is obtained.

• Must meet full criteria for Tourette's Disorder or chronic motor tic disorder.

• Must have failed to respond to an adequate trial, as determined by the investigator, of clonidine, guanfacine, or neuroleptic medication in the past.

• Tics are causing significant distress or impairment, as determined by parent/subject and principal investigator, on current treatment regimen.

• Laboratory results, including serum chemistries, hematology, and urinalysis, must show no significant abnormalities (significant is defined as laboratory values requiring acute medical intervention).

• Must be able to swallow pills.

• Must be of normal intelligence in the judgment of the investigator.

• Must possess an educational level, degree of understanding and command of the English language to enable them to communicate suitably with the investigator and study coordinator, and to understand the nature of the study.

• Subjects and their legal representatives must be considered reliable.

• Written informed consent of parents and subjects (ages 18 and above) and assent of subjects ages 7-17 will be obtained.

Exclusion Criteria:

• Organic brain disease, for example, traumatic brain injury residua.

• Mental retardation as defined by the DSM-IV-TR.

• A history of seizure disorder (other than febrile seizure).

• A history of Sydenham's Chorea.

• Autism, schizophrenia, other psychotic disorder, or bipolar disorder.

• A primary diagnosis of a major mood disorder that requires ongoing psychiatric treatment.

• A neurological disorder other than a tic disorder.

• A major medical illness.

• Females who are of child bearing age who are unwilling to use birth control or who are pregnant, as determined by serum pregnancy test at baseline assessment, or lactating.

• Have a past or current history of substance dependence and/or a current history of substance abuse or who fail baseline toxic screen.

• Have any clinically significant abnormal laboratory result at baseline screening including EKG, or blood tests.

• Have a history of ongoing or previously undisclosed child abuse (risk of removal from home would not allow for consistent caretaker ratings).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Child Study Center	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health

Investigators

• Principal Investigator: Barbara J Coffey, M.D, M.S., NYU School of Medicine, NYU Child Study Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NYU Child Study Center website

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00241176
• Other Study ID Numbers: H12189
• First Posted: Oct 18, 2005
• Last Update Posted: Dec 9, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by NYU Langone Health: Psychiatric; Clinical Trial; Pediatrics; Tourette's Disorder; Tic Disorder
• Additional relevant MeSH terms: Tourette Syndrome; Tic Disorders; Tics; Disease; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Aripiprazole
Arm/Group Description	Subjects received initial dose based on body weight at Visit 2: Subjects between 25-50 kg were started on 1.25 mg/day, Subjects between 50-70 kg were started on 2.5 mg/day, Subjects greater than 70 kg were started on 5 mg/day. Dosage was titrated at Visit 3, 5, 6, or 7 based on YGTSS and CGI-TS ratings at the discretion of the investigator. Subjects who showed evidence of response (reduction in CGI-TS by 1-2 points)remained on the same dose. Subjects who did not show evidence of response could be increased: Subjects between 25-50 kg were could be increased 1.25 mg/day at each titration visit, Subjects between 50-70 kg could be increased 2.5 mg/day at each titration visit, and Subjects greater than 70 kg could be increased 5 mg/day at each titration visit.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sample
Arm/Group Description	Sample of children and adolescents that enrolled in study to receive active medication. This was not a placebo controlled study.
Overall Participants	11
Age (Count of Participants)
<=18 years	10 90.9%
Between 18 and 65 years	1 9.1%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.36 (3.33)
Gender (Count of Participants)
Female	1 9.1%
Male	10 90.9%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Calculating Difference Between Means (Baseline and Endpoint Scores on the Yale Global Tic Severity Scale Subscales)
Description	The Yale Global Tic Severity Scale (YGTSS) is a clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. The maximum YGTSS Global score is 100, while the maximum motor score is 25, the maximum vocal score is 25, and the maximum impairment score is 50. Higher scores indicate more severe tics.
Time Frame	8 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 - Baseline	Group 1 - Endpoint
Arm/Group Description	Sample of children and adolescents that enrolled in study to receive active medication at baseline.	Sample of children and adolescents that enrolled in study to receive active medication at endpoint prior to down titration.
Measure Participants	11	11
YGTSS Motor Tic	15.82 (4.40)	9.73 (2.76)
YGTSS Vocal Tic	12.36 (7.10)	7.00 (5.76)
YGTSS Total Tic	28.18 (7.74)	16.73 (7.54)
YGTSS Global Severity	61.82 (13.49)	33.73 (15.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 - Baseline, Group 1 - Endpoint
	Comments	Group 1 Baseline vs. Endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.003
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	YGTSS Global Severity score (M=61.8 SD=13.49) declined significantly to end point (M=33.7 SD=15.18; p=0.003).

2. Secondary Outcome

Title	Clinical Global Impression Severity Scores
Description	The Clinical Global Impression scale (CGI) is a classic instrument for making global assessments. This scale yields three different measures: 1. Severity of illness (7-point scale, with 7 being the most impaired; assessment of patient's current symptom severity, referred to here as CGIs), 2. Global improvement (7-point scale, with 7 being the most impaired; comparison of patient's baseline condition with his/her current condition, referred to here as CGIi), 3. Efficacy index (4 point x 4 point rating scale, comparison of patient's baseline condition with a ratio of current therapeutic benefit to severity of side effects)
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 - Baseline	Group 1 - Endpoint
Arm/Group Description	Sample of children and adolescents that enrolled in study to receive active medication at baseline.	Sample of children and adolescents that enrolled in study to receive active medication at endpoint prior to down titration.
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	4.45 (0.52)	3.18 (0.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 - Baseline, Group 1 - Endpoint
	Comments	Mean scores baseline to endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.004
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean (SD) CGI-Tic severity scores reduced significantly from (M=4.45 SD=0.52) (moderate-marked) at baseline to (M=3.18 SD =0.60) (mild) at end point ( p=0.004).

Adverse Events

Arm/Group Title	Sample
Arm/Group Description	Sample of children and adolescents that enrolled in study to receive active medication. This was not a placebo controlled study.
All Cause Mortality
	Sample
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sample
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Sample
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Gastrointestinal disorders
Stomach discomfort	9/11 (81.8%)	26
General disorders
Headache	11/11 (100%)	34
Appetite increase/weight gain	7/11 (63.6%)	27
Tiredness/fatigue	8/11 (72.7%)	23
Dizziness	9/11 (81.8%)	18
Appetite decrease/weight loss	6/11 (54.5%)	12
Drowsiness/sedation	7/11 (63.6%)	13
Dry mouth	4/11 (36.4%)	10
Musculoskeletal and connective tissue disorders
Muscle, bone, or joint pain condition	10/11 (90.9%)	31

Limitations/Caveats

All subjects failed to respond to previous tic medications so could have unique tic symptoms, small sample size, and this was an open-label study, so we did not have a comparison group nor were we blinded to treatment.

More Information

Certain Agreements

All Principal Investigators ARE 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.