Double Blinded, Placebo-Controlled Trial of Paliperidone Addition in SRI-Resistant Obsessive-Compulsive Disorder

• Sponsor: University of South Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT00632229
• Collaborator: Indiana University (Other), Ortho-McNeil Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 34
• Locations: 2
• Arms: 2
• Duration (Months): 71
• Patients Per Site: 17
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established treatments for OCD are a specific form of Cognitive Behavioral Therapy (CBT) and the Serotonin Reuptake Inhibitor medications (SRIs). Few patients with OCD experience complete symptom resolution with either modality and even after two consecutive SRI trials, as many as 30%-40% of patients fail to derive a satisfactory response. Pharmacological options for these SRI-resistant cases include switching to a different antidepressant, increasing the dose of SRI, or augmentation with another agent.

Previous studies showed that approximately 33-50% of OCD patients who have not had an adequate response to SRI medication had a positive response when an atypical antipsychotic medication was added. However, the problematic acute and long-term side effects of these medications are of concern and, at times, limit their use. Paliperidone has a number of advantages over these medications including fewer drug interactions and better tolerability. Thus, this study is designed to determine whether paliperidone augmentation of an existing medication is effective relative to taking a placebo and your existing medication.

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

Detailed Description

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for OCD are a specific form of Cognitive Behavioral Therapy (CBT) and the Serotonin Reuptake Inhibitors (SRIs). Few patients with OCD experience complete symptom resolution with either modality. Even after two consecutive adequate SRI trials, as many as 30%-40% of patients fail to derive a satisfactory response. Pharmacological options for these SRI-resistant cases include switching to a different antidepressant, increasing the dose of SRI, or augmentation with another agent.

Among the pharmacological augmentation strategies, adjunctive antipsychotic medications enjoy the most empirical support as well as wide-scale use in clinical practice. Utilizing IMS Health's National Disease and Therapeutic Index (NDTI) for 12 months ending in November 2004, 4.2% of antipsychotic medication use is for anxiety and 1.3% specifically for OCD. Conversely, for OCD patients, antipsychotic medications account for 8.6% of drug use (IMS Health NDTI MAT, 2004). Among pediatric patients, prescriptions of antipsychotics increased from 8.6 out of 1,000 U.S. children in 1995-1996 to 39.4 out of 1,000 children in 2001-2002 (Cooper et al., 2006). Similarly, Medco, a private insurance company, noted that the rate of children 19 years and under covered by private insurance with at least one atypical prescription jumped 80% from 2001 to 2005 - from 3.6 per 1,000 to 6.5 per 1,000 (USA Today, extracted 5/2/2006). These rates parallel our own research, in which approximately 35% of adult patients on psychotropics were taking an antipsychotic in addition to their SRI. Thus, clearly there is a large sample of OCD patients that are being prescribed atypical antipsychotics to augment other treatments.

Previous studies showed that approximately 33-50% of OCD patients who have not had an adequate response to SRI medication had a positive response when an atypical antipsychotic medication was added (Bloch et al., 2006). Risperidone has been the most studied agent and has the most consistently positive findings (e.g., McDougle et al., 2000). However, the problematic acute and long-term side effects of risperidone (and other atypicals) are of concern and, at times, limit their use. Paliperidone, a metabolite of risperidone that utilizes OROS osmotic drug-release technology, has a number of advantages over risperidone including a lack of drug x drug interactions and a predictable pharmacokinetic profile that is associated with better tolerability. Thus, paliperidone has the potential to be a safer alternative for augmentation in OCD patients pending supporting efficacy data. Given the need to examine the efficacy of paliperidone, this protocol is designed to determine whether paliperidone augmentation of an SRI is effective relative to a placebo-control, and safe/tolerable in patients with OCD who have not adequately responded to past adequate SRI treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double Blinded, Placebo-Controlled Trial of Paliperidone Addition in SRI-Resistant Obsessive-Compulsive Disorder
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paliperidone Recieves study medication called paliperidone	Drug: Paliperidone; Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.; Other Names: Invega
Placebo Comparator: Pill placebo Placebo comparator	Drug: Placebo; Pill placebo taken daily ranging from 3-9mg/day depending on tolerability and efficacy.

Outcome Measures

Primary Outcome Measures

1. Yale Brown Obsessive Compulsive Scale [End of study (8 weeks)]

   This measure assesses obsessive-compulsive symptom severity across 10 items that are completed during an interview format with the person with OCD. These 10 items are summed to derive a total score, which ranges from 0-40 [Scale range: 0 (Minimum) - 40 (Maximum)] with higher scores corresponding to more severe obsessive-compulsive symptoms.

Secondary Outcome Measures

1. Clinical Global Impressions - Severity of Obsessive-Compulsive Symptoms [post-treatment]

   This assessment measures the overall severity of obsessive-compulsive symptoms. It consists of a single item that is completed by a clinician with scores ranging from 0-6 with higher scores corresponding with more severe obsessive-compulsive symptoms. Thus, higher scores represent a worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Meets DSM-IV-TR criteria for a principal current diagnosis of OCD which is confirmed by both clinical evaluation and by structured interviews. OCD subjects with other comorbidities will be included provided OCD is judged to be the chief complaint.

2. Subjects must continue to experience clinically significant symptoms of OCD (Y-BOCS score ≥19 and a rating of "moderate" or greater on the Clinical Global Impressions (CGI) scale) despite at least two adequate SRI monotherapy trials. One unsatisfactory trial can include the SRI currently being taken by the patient provided that the duration of treatment is 12 weeks or more and that the dose has been adequate. Subjects must be taking a clinically effective dose of a SRI (i.e., clomipramine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) for at least 12 weeks. Subjects must be on their current dose for at least 12 weeks and must maintain their current dose throughout the study.

3. Between the ages of 18-70 years of age.

4. Only subjects with OC symptoms of at least one-year duration will be included.

5. Eligible subjects must be in good physical health. Screening procedures will include detailed medical history, complete physical and neurological exams, routine blood studies (CBC, liver function tests, electrolytes), ECG, urine toxicology screen, and serum pregnancy test in women of child-bearing potential.

Exclusion Criteria:

1. Primary depression, schizophrenia or other psychotic disorders.

2. Active bipolar disorder.

3. Non-responder in the past to atypical antipsychotic augmentation. This criterion was chosen to prevent recruiting a sample of chronically refractory OCD cases that would otherwise be suited for more extreme interventions such as deep brain stimulation.

4. Non-responder in the past to an adequate trial (> 20 hours) of cognitive-behavioral therapy that will be assessed by records review.

5. Current clinically significant suicidality or individuals who have engaged in suicidal behaviors within 6 months will be excluded and referred for appropriate clinical intervention.

6. Alcohol or other significant substance abuse within the last 6 months.

7. History of neurosurgery, encephalitis or significant head trauma or a significant medical condition such as heart, liver, or renal disease.

8. Nursing mothers or women of childbearing potential who do not use adequate contraception will be excluded.

9. Subjects at an increased risk for seizures will also be excluded from this study (e.g., subjects with a history of seizures [other than childhood febrile seizures], subjects taking concomitant medications known to lower the seizure threshold).

10. Estimated IQ < 80, mental retardation, dementia, brain damage, or other cognitive impairment that would interfere with the capacity to participate in the study and complete measures. If needed, the WASI will be used to assess this at screening.

11. Concurrent use of benzodiazepines, other than for treatment of insomnia, will be prohibited during the trial. No other psychotropic medications will be permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Florida	St. Petersburg	Florida	United States	33701
2	University Hospital Outpatient Center, Psychiatry	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• University of South Florida
• Indiana University
• Ortho-McNeil Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Eric A Storch, Ph.D., University of South Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00632229
• Other Study ID Numbers: USF 08-0100
• First Posted: Mar 10, 2008
• Last Update Posted: Feb 6, 2014
• Last Verified: Oct 1, 2013

• Keywords provided by University of South Florida: Obsessive-Compulsive Disorder; Adults; Medication; Treatment
• Additional relevant MeSH terms: Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Paliperidone Palmitate

Study Results

Participant Flow

Recruitment Details	Thirty-four adults with a principal diagnosis of OCD were recruited between May 2008 and March 2012.

Arm/Group Title	Paliperidone	Placebo
Arm/Group Description	Recieves study medication Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.	Placebo comparator Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.
Period Title: Overall Study
STARTED	17	17
COMPLETED	11	11
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Paliperidone	Placebo	Total
Arm/Group Description	Recieves study medication Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.	Placebo comparator Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.	Total of all reporting groups
Overall Participants	17	17	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	16 94.1%	33 97.1%
>=65 years	0 0%	1 5.9%	1 2.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.59 (9.99)	45.7 (12.27)	43.7 (11.4)
Sex: Female, Male (Count of Participants)
Female	9 52.9%	10 58.8%	19 55.9%
Male	8 47.1%	7 41.2%	15 44.1%
Region of Enrollment (participants) [Number]
United States	17 100%	17 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Yale Brown Obsessive Compulsive Scale
Description	This measure assesses obsessive-compulsive symptom severity across 10 items that are completed during an interview format with the person with OCD. These 10 items are summed to derive a total score, which ranges from 0-40 [Scale range: 0 (Minimum) - 40 (Maximum)] with higher scores corresponding to more severe obsessive-compulsive symptoms.
Time Frame	End of study (8 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone	Placebo
Arm/Group Description	Recieves study medication Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.	Placebo comparator Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.
Measure Participants	17	17
Mean (Standard Deviation) [Scores on a scale]	19.14 (11.13)	21.24 (8.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone, Placebo
	Comments	To evaluate between-group continuous outcomes of the pilot controlled trial, ANCOVAs were performed, where 8-week outcome scores were predicted by treatment condition while covarying for baseline scores.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Clinical Global Impressions - Severity of Obsessive-Compulsive Symptoms
Description	This assessment measures the overall severity of obsessive-compulsive symptoms. It consists of a single item that is completed by a clinician with scores ranging from 0-6 with higher scores corresponding with more severe obsessive-compulsive symptoms. Thus, higher scores represent a worse outcome.
Time Frame	post-treatment

Outcome Measure Data

Analysis Population Description

Includes those subjects who were randomized to their respective condition.

Arm/Group Title	Paliperidone	Placebo
Arm/Group Description	Recieves study medication Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.	Placebo comparator Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.
Measure Participants	17	17
Mean (Standard Deviation) [Scores on a scale]	4.09 (1.66)	4.21 (1.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone, Placebo
	Comments	To evaluate between-group continuous outcomes of the pilot controlled trial, ANCOVAs were performed, where 8-week outcome scores were predicted by treatment condition while covarying for baseline scores.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Paliperidone		Placebo
Arm/Group Description	Recieves study medication Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.		Placebo comparator Paliperidone : Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.
All Cause Mortality
	Paliperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Paliperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Paliperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)		12/17 (70.6%)
Ear and labyrinth disorders
Ear Ringing	2/17 (11.8%)		2/17 (11.8%)
Eye disorders
blurred vision	3/17 (17.6%)		1/17 (5.9%)
Gastrointestinal disorders
dry mouth	4/17 (23.5%)		3/17 (17.6%)
Nausea	0/17 (0%)		3/17 (17.6%)
Constipation	5/17 (29.4%)		1/17 (5.9%)
Diarrhea	1/17 (5.9%)		2/17 (11.8%)
Increased Appetite	5/17 (29.4%)		3/17 (17.6%)
Decreased Appetite	1/17 (5.9%)		1/17 (5.9%)
General disorders
Somnolence	7/17 (41.2%)		8/17 (47.1%)
Insomnia	5/17 (29.4%)		5/17 (29.4%)
Agitation	4/17 (23.5%)		2/17 (11.8%)
Nervous system disorders
Headache	4/17 (23.5%)		6/17 (35.3%)
Dizziness	3/17 (17.6%)		4/17 (23.5%)
Lightheadness	3/17 (17.6%)		3/17 (17.6%)
Muscle Stiffness	4/17 (23.5%)		0/17 (0%)
Shakiness	1/17 (5.9%)		1/17 (5.9%)
Psychiatric disorders
Anxiety	1/17 (5.9%)		1/17 (5.9%)
Renal and urinary disorders
Increased need to urinate	4/17 (23.5%)		1/17 (5.9%)
Reproductive system and breast disorders
Galactorrhea	2/17 (11.8%)		0/17 (0%)

Limitations/Caveats

Modest sample and analyses were potentially underpowered to detect between-group differences on OCD measures. It was not possible to determine response from participants' current medication. Little racial/ethnic and socioeconomic variability

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.