Determining Metabolic Effects of Valproate and Antipsychotic Therapy

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00167934
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 164
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

This study will determine the metabolic processes responsible for high levels of blood glucose, metabolism disorders, and weight gain in people with schizophrenia who have been treated with antipsychotic medications in combination with valproate.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Valproate; Drug: Placebo	N/A

Detailed Description

This project aims to study the whole-body metabolic processes responsible for hyperglycemia, dyslipidemia and increased adiposity in schizophrenia patients treated with antipsychotic medications in combination with valproate. The project hypothesizes that combined treatment with valproate and antipsychotic medications will decrease insulin sensitivity at the level of skeletal muscle, liver and adipose tissue, in comparison to antipsychotic monotherapy. The decrease in insulin sensitivity is hypothesized to be associated with defects in glucose and lipid metabolism and increased adiposity

Treatment effects of antipsychotic/valproate combination therapy on different components of insulin secretion and action, and treatment effects on abdominal versus peripheral adiposity, are unknown despite the availability of gold-standard methods and the prognostic significance of these issues. Relevant data are needed to target basic research, to identify the potential for acute and long-term complications, and to plan therapeutic interventions. The following specific aims will be addressed in non-diabetic schizophrenia patients treated with atypical antipsychotics who will be randomized to open label treatment with either valproate or no adjuvant. Evaluations are performed at baseline and 3 months of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Metabolic Effects of Valproate and Antipsychotic Therapy
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 50% of participants will receive placebo	Drug: Placebo; Placebo given at same frequency as Valproate
Experimental: Experimental 50% of participants will receive Depakote ER	Drug: Valproate; Depakote ER 500 mg to 3000 mg taken every night; Other Names: Depakote ER

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks [Measured at baseline and Week 12]

   Change in body composition (total body fat) was assessed using dual energy x-ray absorptiometry

2. Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal) [Measured at baseline and Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets DSM-IV criteria for schizophrenia, any type, treated with the same antipsychotic for at least 6 months

• No antipsychotic medication dose changes for 1 month, and no other medication changes for 1 month prior to study entry

Exclusion Criteria:

• Meets DSM-IV criteria for substance abuse within 3 months of study entry

• Involuntary legal status (as per Missouri law)

• Any serious medical disorder that may confound the assessment of relevant biologic measures or diagnosis, including: significant organ system dysfunction, metabolic diseases, type 1 or 2 diabetes mellitus, pregnancy, endocrine disease, coagulopathy, anemia, or acute infection

• Currently taking more than one antipsychotic medication

• Currently taking prescription medications (except certain psychotropic medications as discussed below), including oral contraceptive pills, any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Dan W. Haupt, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for the Washington University Department of Psychiatry

Publications

• Haupt DW, Newcomer JW. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001;62 Suppl 27:15-26; discussion 40-1. Review.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00167934
• Other Study ID Numbers: K23MH067795; K23MH067795; DAHBR AK-TNET1
• First Posted: Sep 14, 2005
• Last Update Posted: Feb 10, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Washington University School of Medicine: Diabetes; Metabolic
• Additional relevant MeSH terms: Schizophrenia; Valproic Acid

Study Results

Participant Flow

Arm/Group Title	Placebo	Experimental
Arm/Group Description	50% of participants will receive placebo	50% of participants will receive Depakote ER
Period Title: Overall Study
STARTED	82	82
COMPLETED	82	82
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Experimental	Total
Arm/Group Description	50% of participants will receive placebo	50% of participants will receive Depakote ER	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.6 (10.1)	41.3 (8.4)	40.9 (9.2)
Sex: Female, Male (Count of Participants)
Female	7 28%	6 24%	13 26%
Male	18 72%	19 76%	37 74%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	6 24%	7 28%	13 26%
African American	19 76%	18 72%	37 74%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks
Description	Change in body composition (total body fat) was assessed using dual energy x-ray absorptiometry
Time Frame	Measured at baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Experimental
Arm/Group Description	50% of participants will receive placebo	50% of participants will receive Depakote ER
Measure Participants	24	22
Mean (Standard Deviation) [percent change]	-0.51 (2.13)	2.03 (2.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Experimental
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal)
Time Frame	Measured at baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Experimental
Arm/Group Description	50% of participants will receive placebo	50% of participants will receive Depakote ER
Measure Participants	25	25
Mean (Standard Deviation) [percent change]	0.27 (1.23)	-0.35 (1.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Experimental
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	At 12 Week Assessment
Adverse Event Reporting Description	An Adverse Event Form is administered to participants by a trained rater.
Arm/Group Title	Placebo		Experimental
Arm/Group Description	50% of participants will receive placebo		50% of participants will receive Depakote ER
All Cause Mortality
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		12/24 (50%)
General disorders
Drowsiness/Somnolence	1/23 (4.3%)		2/24 (8.3%)
Tiredness/Fatigue	0/23 (0%)		3/24 (12.5%)
Anxiety	1/23 (4.3%)		2/24 (8.3%)
Restlessness	2/23 (8.7%)		2/24 (8.3%)
Tremor	0/23 (0%)		3/24 (12.5%)

Limitations/Caveats

[Not Specified]

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.