Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression

• ClinicalTrials.gov Identifier: NCT00194116
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Results First Posted: July 17, 2019
• Last Update Posted: July 17, 2019
• Sponsor: University Hospitals Cleveland Medical Center
• Collaborator: Abbott
• Information provided by (Responsible Party): Keming Gao, University Hospitals Cleveland Medical Center

Study Description

Brief Summary:

Double-Blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression Previously Diagnosed and Treated as Recurrent Major Depression: This study recruits males and females aged 18 - 70 who currently meet diagnostic criteria for bipolar I or bipolar II disorder and are currently experiencing an episode of major depression. Patients are randomized to double-blind treatment with divalproex sodium ER or placebo and remain in the study for up to six weeks. This six-week double-blind treatment period is followed by an open-label treatment period of six months duration. This study is sponsored by Abbott Laboratories.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder	Drug: Divalproex Sodium ER; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression
• Study Start Date: September 2004
• Actual Primary Completion Date: October 2007
• Actual Study Completion Date: February 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Divalproex Sodium ER	Drug: Divalproex Sodium ER; Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.; Other Name: Depakote ER
Placebo Comparator: Placebo	Drug: Placebo; . Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.

Outcome Measures

Primary Outcome Measures :

1. Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Acute phase (week0-week6) ]
   MADRS total scores range from 0-60, where higher scores are indicative of more depression.

Secondary Outcome Measures :

1. Change in Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Acute phase (week0-week6) ]
   YMRS Scores range from 0 to 60 where higher scores are indicative of more mania.
2. Change in General Behavior Inventory (GBI) Depression Scale Score [ Time Frame: Acute phase (week0-week6) ]
   GBI Depression Scale Scores range from 46-184, where higher scores are indicative of more depression.
3. Change in General Behavior Inventory (GBI) Hypomanic/Biphasic Scale Score [ Time Frame: Acute phase (week0-week6) ]
   GBI Hypomanic/Biphasic Scale scores range from 28-112, where higher scores are indicative of more hypomanic/manic symptoms.
4. Change in Short Form Health Survey (SF-36) Physical Component Summary Score [ Time Frame: Acute phase (week0-week6) ]
   SF-36 Physical Component Summary scores range from 0-100, with a higher score indicating better physical health.
5. Change in Short Form Health Survey (SF-36) Mental Component Summary Score [ Time Frame: Acute phase (week0-week6) ]
   SF-36 Mental Component Summary scores range from 0-100, with a higher score indicating better mental health.
6. Change in Hamilton Anxiety Rating Scale (HAMA) Total Score [ Time Frame: Acute phase (week0-week6) ]
   HAMA Scores range from 0 to 56 where higher scores are indicative of more anxiety.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subject must give consent to participate in the study and sign and date the IRB approved written informed consent form prior to the initiation of any study procedures
• Subject must be between the ages of 18 and 70
• Subject must have a diagnosis of bipolar I or II.
• Subject must be currently depressed as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Subject must have a baseline Montgomery-Asberg Depression Scale (MADRS) score of >19 and Young Mania Rating Scale (YMRS) score of <12
• Women of childbearing potential must be nonpregnant/nonlactating and using adequate contraception if sexually active
• Subject must not be using any concomitant psychotropic medications during the acute phase except prn benzodiazepines

Exclusion Criteria:

• Subjects lacks the capacity to provide informed consent
• Subject has currently or previously used divalproex or Dvpx-ER
• Subject is a serious suicide risk or has medically unstable conditions as judged by the investigators
• Subject has any alcohol, cocaine, or cannabis dependence within 3 months of study entry
• Subject has any cocaine, hallucinogens, opiates, crystal methamphetamine, or MMDA abuse within 3 months of study entry

Contacts and Locations

Locations

United States, Ohio

University Hospitals of Cleveland

Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

University Hospitals Cleveland Medical Center

Abbott

Investigators

• Principal Investigator: Keming Gao, MD, PhD; Case Western Reserve University / University Hospitals of Cleveland

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Muzina DJ, Gao K, Kemp DE, Khalife S, Ganocy SJ, Chan PK, Serrano MB, Conroy CM, Calabrese JR. Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naive bipolar I or II depression: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011 Jun;72(6):813-9. doi: 10.4088/JCP.09m05570gre. Epub 2010 Aug 24.

• Responsible Party: Keming Gao, Director, Mood and Anxiety Clinic, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT00194116
• Other Study ID Numbers: UHHS 08-03-07
• First Posted: September 19, 2005
• Results First Posted: July 17, 2019
• Last Update Posted: July 17, 2019
• Last Verified: May 2019

Additional relevant MeSH terms:

Bipolar Disorder; Bipolar and Related Disorders; Mental Disorders; Valproic Acid; Anticonvulsants; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; GABA Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs