PAMS: Side Effect Study of Antipsychotic Medicines to Treat Childhood Bipolar Disorder

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00746252
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to learn more about weight gain and related side effects when children are treated with antipsychotic medicine for mood disorders.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: risperidone; Drug: aripiprazole	N/A

Detailed Description

This protocol is a six month, randomized, open label trial of risperidone versus aripiprazole in antipsychotic naive youth (7 - 12 years old) who have been identified by their clinical treatment provider as needing antipsychotic treatment of a bipolar disorder.

This study proposes to monitor changes in metabolic parameters (body mass index percentile, % body fat, insulin resistance, and lipid levels) over the course of six months treatment with aripiprazole or risperidone in youth with a bipolar spectrum disorder. We will also assess possible mechanisms of second generation antipsychotic induced weight gain by monitoring physical activity and hunger/appetite changes over the course of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Investigating Metabolic Side Effects of Antipsychotic Medications in Children
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 risperidone	Drug: risperidone; Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.; Other Names: Brand name: Risperdal
Experimental: 2 aripiprazole	Drug: aripiprazole; children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.; Other Names: Brand name: Abilify

Outcome Measures

Primary Outcome Measures

1. Weight Gain [These measurements are done biweekly from baseline up until 12 weeks]

   Weight gain from baseline to last observation up to 12 weeks. Last observation carried to 12 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• We will include children, ages 7 - 12 years old, male and female with diagnosis of a bipolar spectrum disorder.

• Specific diagnoses included are as follows:

• Bipolar I disorder,

• Bipolar II disorder,

• Bipolar Disorder Not Otherwise Specified,

• Mood Disorder Not otherwise specified.

• The inclusion of a spectrum of bipolar diagnosis is because children with moderate to severe impairment from mood symptoms often still do not meet criteria for Bipolar I disorder since young children tend to have more chronic (non-episodic) course of symptoms and diagnostic criteria for Bipolar I disorder are more difficult to apply to adults than young children (e.g. symptoms of grandiosity and euphoria).

• No prior treatment with an antipsychotic medication for >30 days. This criteria was added because weight loss on an assigned treatment may be due to discontinuing a prior antipsychotic medication rather than due to the current treatment.

• Recommendation from a current psychiatric treatment provider for treatment with an antipsychotic medication.

• This inclusion criteria provides an added layer of safety in that youth who have referred for the study have already been deemed by their independent provider to need an antipsychotic medication, so we are only exposing children to antipsychotic treatment who would have been treated with this type of medication regardless of whether or not there care was provided in a research or clinical program.

Exclusion Criteria:

• Medications: We will exclude children who are on current treatment with

• oral steroids,

• lithium,

• depakote since these medications will have a confounding effect on weight.

• We will allow children on stimulant medication to participate, because ADHD comorbidity is very high in prepubertal bipolar disorder (unlike adolescent or adult onset bipolar disorder).

• We are including ADHD children to thus increase generalizability of the study, and it would be inappropriate to withhold stimulant treatment from these children for a six month period.

• Recruitment will be stratified to make sure there are equal numbers of patients on stimulants in each group.

• Somatic Conditions: We will exclude children with diabetes (type I or type II), and those with physical disability that would interfere with physical activity (will specifically exclude children whose guardian reports that the child has been medically excused from physical education at their school program because of physical disability) since insulin sensitivity and activity levels are outcome measures being assessed in this protocol.

• We will exclude youth with mental retardation, by parent report. Cognitive screening will be done with the Wechsler Abbreviated Scale of Intelligence (WASI).

• Youth with an IQ less than 70 will be excluded because they may have difficulty with self report measures.

• We will exclude children who have a history of treatment of an antipsychotic medication for >30 days, as explained above.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland, School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

• Principal Investigator: Gloria Reeves, M.D., University of Maryland, Baltimore

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gloria Reeves, Associate Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00746252
• Other Study ID Numbers: HP-00043695
• First Posted: Sep 3, 2008
• Last Update Posted: Jan 6, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Gloria Reeves, Associate Professor, University of Maryland, Baltimore: bipolar; children; antipsychotic; side effect
• Additional relevant MeSH terms: Bipolar Disorder; Risperidone; Aripiprazole

Study Results

Participant Flow

Pre-assignment Detail	Two participants enrolled and completed baseline assessments but were withdrawn from the study at baseline due to the following reasons: Abnormal glucose tolerance test requiring further assessment with endocrinology. Unable to complete lab work due to increased distress.

Arm/Group Title	Risperidone	Aripiprazole
Arm/Group Description	risperidone risperidone: Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.	aripiprazole aripiprazole: children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.
Period Title: Overall Study
STARTED	1	2
COMPLETED	0	0
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Risperidone	Aripiprazole	Total
Arm/Group Description	risperidone risperidone: Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.	aripiprazole aripiprazole: children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.	Total of all reporting groups
Overall Participants	1	2	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.75 (0)	12.5 (0)	10.9 (2.78)
Sex: Female, Male (Count of Participants)
Female	1 100%	2 100%	3 100%
Male	0 0%	0 0%	0 0%
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%	2 100%	2 66.7%
White	1 100%	0 0%	1 33.3%
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	1 100%	2 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Weight Gain
Description	Weight gain from baseline to last observation up to 12 weeks. Last observation carried to 12 weeks.
Time Frame	These measurements are done biweekly from baseline up until 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone	Aripiprazole
Arm/Group Description	risperidone risperidone: Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.	aripiprazole aripiprazole: children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.
Measure Participants	1	2
Mean (Standard Deviation) [pounds]	8.5 (NA)	6.65 (1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone, Aripiprazole
	Comments	Comparison of mean weight gain between groups.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.495
	Comments	Threshold of significance is p<.05
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Risperidone		Aripiprazole
Arm/Group Description	risperidone risperidone: Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.		aripiprazole aripiprazole: children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.
All Cause Mortality
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		2/2 (100%)
Metabolism and nutrition disorders
Weight gain	1/1 (100%)	1	2/2 (100%)	2

Limitations/Caveats

The study funding stopped before a sufficient number of participants could be enrolled and therefore the study was terminated. Additionally the stopping criteria of 5% weight gain limited the length of time participants were in the study.

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.