GERI-BD: Treatment of Bipolar Mania in Older Adults

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00254488
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 224
• Locations: 8
• Arms: 2
• Duration (Months): 69
• Patients Per Site: 28
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will compare the benefits and side effects of lithium and divalproex in the treatment of older adults with bipolar mania.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Mania	Drug: Lithium (LI); Drug: Divalproex (DV)	Phase 4

Detailed Description

This is the first controlled acute treatment study of bipolar disorder in adults 60 years or older with current DSM-IV manic, mixed, or hypomanic episodes. The number of older adults with severe and disabling bipolar disorder is increasing, and information to guide the management of the treatment of the disease is lacking in this population. Guidelines for treatment of younger people with bipolar disorder cannot be used for older people, and there are no safety and efficacy data upon which to base initial treatment decisions for older patients with bipolar mania. Mood stabilizers (lithium and divalproex) are the first-line treatment for bipolar disorder. However, in aged patients physiological changes and comorbid diseases may increase vulnerability to side effects and limit the benefits of the medications.

This double-blind study will compare the benefits and side-effects of 9 weeks of treatment with lithium and divalproex in people with bipolar mania. Participants, who may be treated during inpatient hospitalization or as outpatients, will be randomly assigned to receive either lithium or divalproex. During the first 3 weeks of treatment careful titration of lithium and divalproex will be done to reach dose ranges. All other psychotropic medications will be discontinued. Behavioral interventions and/or lorazepam may be added, if necessary. After the first 3 weeks, if symptoms do not improve, risperidone will be added to be taken everyday with the study medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Acute Pharmacotherapy of Late-Life Mania (GERI-BD)
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lithium (LI) Participants will receive 9 weeks of treatment with lithium	Drug: Lithium (LI); The starting LI dose will be 150 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma LI level ranges between 0.40 and 0.99 mEq/L (target 0.80 to 0.99 mEq/L).; Other Names: Depakote
Experimental: Divalproex (DV) Participants will receive 9 weeks of treatment with divalproex	Drug: Divalproex (DV); Dosage of DV will be 250 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma DV level ranges between 40 and 99 mcg/mL (target 80 to 99 mcg/ml).; Other Names: Valproate

Outcome Measures

Primary Outcome Measures

1. Sedation Score [Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9]

   The Sedation Item score of the UKU (Norwegian for Committee of Clinical Investigations) Side Effect Rating Scale. A higher value indicates greater severity. Range is 0-3 (not present, mild, moderate, or severe).

2. Young Mania Rating Scale (YMRS) Scores [Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9]

   The Young Mania Rating Scale is an eleven item interviewer-rated instrument. Four items are scored 0-8, the others 0-4. The total score therefore ranges from 0-60, with higher values reflecting greater severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of DSM-IV Bipolar Disorder, Type I: current manic, mixed, or hypomanic episodes

Exclusion Criteria:

• Rapid cycling bipolar disorder

• History of substance abuse or dependence within last 3 months

• Diagnosis of schizophrenia or other chronic psychotic conditions

• Acute or unstable medical illness

• Documented intolerance to Lithium, Depakote, Risperidone, or Lorazepam

• Dementia

• Inability to communicate in English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Precise Research Centers	Flowood	Mississippi	United States	39232
2	Weill Cornell Medical College	White Plains	New York	United States	10605
3	Duke University Medical Center	Durham	North Carolina	United States	27710
4	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
7	Baylor College of Medicine	Houston	Texas	United States	77030
8	Centre for Addiction and Mental Health	Toronto	Ontario	Canada	M6J1H4

Sponsors and Collaborators

• Weill Medical College of Cornell University
• National Institute of Mental Health (NIMH)

Investigators

• Study Chair: Robert Young, MD, Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00254488
• Other Study ID Numbers: U01MH068847; U01MH068847
• First Posted: Nov 16, 2005
• Last Update Posted: Sep 25, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Mania; Bipolar Disorder; Valproic Acid

Study Results

Participant Flow

Arm/Group Title	Lithium	Divalproex
Arm/Group Description	Participants will receive 9 weeks of treatment with lithium Lithium (LI): The starting LI dose will be 150 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma LI level ranges between 0.40 and 0.99 mEq/L (target 0.80 to 0.99 mEq/L).	Participants will receive 9 weeks of treatment with divalproex Divalproex (DV): Dosage of DV will be 250 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma DV level ranges between 40 and 99 mcg/mL (target 80 to 99 mcg/ml).
Period Title: Overall Study
STARTED	112	112
COMPLETED	55	63
NOT COMPLETED	57	49

Baseline Characteristics

Arm/Group Title	Lithium (LI)	Divalproex (DV)	Total
Arm/Group Description	Participants will receive 9 weeks of treatment with Lithium. The starting Lithium dose will be 150 mg in the morning and evening.	Participants will receive 9 weeks of treatment with Divalproex. The starting Divalproex dose will be 250 mg in the morning and evening.	Total of all reporting groups
Overall Participants	112	112	224
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.6 (6.8)	68.3 (6.1)	68.0 (6.4)
Sex: Female, Male (Count of Participants)
Female	56 50%	59 52.7%	115 51.3%
Male	56 50%	53 47.3%	109 48.7%
Young Mania Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.1 (7.4)	25.5 (6.1)	26.3 (6.8)
Sedation score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	.5 (.7)	.5 (.6)	.5 (.65)

Outcome Measures

1. Primary Outcome

Title	Sedation Score
Description	The Sedation Item score of the UKU (Norwegian for Committee of Clinical Investigations) Side Effect Rating Scale. A higher value indicates greater severity. Range is 0-3 (not present, mild, moderate, or severe).
Time Frame	Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9

Outcome Measure Data

Analysis Population Description

The number of participants analyzed over the course of the study decreases due to participants missing a visit or dropping from the study.

Arm/Group Title	Lithium (LI)	Divalproex (DV)
Arm/Group Description	Participants will receive 9 weeks of treatment with Lithium. The starting Lithium dose will be 150 mg in the morning and evening.	Participants will receive 9 weeks of treatment with Divalproex. The starting Divalproex dose will be 250 mg in the morning and evening.
Measure Participants	107	109
Day 4	0.5 (0.7)	0.5 (0.7)
Day 9	0.6 (0.7)	0.6 (0.6)
Day 15	0.4 (0.6)	0.5 (0.7)
Week 3	0.5 (0.7)	0.6 (0.7)
Week 4	0.5 (0.7)	0.5 (0.6)
Week 5	0.5 (0.7)	0.4 (0.6)
Week 6	0.5 (0.7)	0.5 (0.6)
Week 7	0.4 (0.6)	0.4 (0.5)
Week 8	0.4 (0.6)	0.3 (0.5)
Week 9	0.4 (0.6)	0.4 (0.6)

2. Primary Outcome

Title	Young Mania Rating Scale (YMRS) Scores
Description	The Young Mania Rating Scale is an eleven item interviewer-rated instrument. Four items are scored 0-8, the others 0-4. The total score therefore ranges from 0-60, with higher values reflecting greater severity.
Time Frame	Day 4, Day 9, Day 15, and then Weekly from Week 3 to Week 9

Outcome Measure Data

Analysis Population Description

The number of participants analyzed over the course of the study decreases due to participants missing a visit or dropping from the study.

Arm/Group Title	Lithium (LI)	Divalproex (DV)
Arm/Group Description	Participants will receive 9 weeks of treatment with Lithium. The starting Lithium dose will be 150 mg in the morning and evening.	Participants will receive 9 weeks of treatment with Divalproex. The starting Divalproex dose will be 250 mg in the morning and evening.
Measure Participants	108	109
Day 4	21.4 (9.3)	19.7 (7.7)
Day 9	19.0 (9.5)	16.3 (8.1)
Day 15	14.3 (9.3)	15.2 (8.7)
Week 3	12.1 (8.8)	13.1 (9.4)
Week 4	9.4 (5.9)	9.9 (7.1)
Week 5	7.6 (5.8)	9.8 (7.0)
Week 6	7.2 (5.4)	8.2 (6.5)
Week 7	6.0 (6.0)	7.0 (5.9)
Week 8	6.0 (5.4)	6.7 (5.8)
Week 9	6.3 (6.0)	6.8 (5.9)

Adverse Events

Time Frame	9 weeks
Adverse Event Reporting Description	Clinicaltrials.gov definitions apply.
Arm/Group Title	Lithium (LI)		Divalproex (DV)
Arm/Group Description	Participants will receive 9 weeks of treatment with lithium. Lithium (LI): The starting LI dose will be 150 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma LI level ranges between 0.40 and 0.99 mEq/L (target 0.80 to 0.99 mEq/L).		Participants will receive 9 weeks of treatment with divalproex. Divalproex (DV): Dosage of DV will be 250 mg in the morning and evening. The dose of medication will be adjusted to achieve plasma DV level ranges between 40 and 99 mcg/mL (target 80 to 99 mcg/ml).
All Cause Mortality
	Lithium (LI)		Divalproex (DV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/112 (0%)		2/112 (1.8%)
Serious Adverse Events
	Lithium (LI)		Divalproex (DV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/112 (21.4%)		22/112 (19.6%)
Blood and lymphatic system disorders
Hospitalization for cellulitis	0/112 (0%)	0	1/112 (0.9%)	1
Cardiac disorders
Chest pain	2/112 (1.8%)	2	1/112 (0.9%)	1
Hypertension	1/112 (0.9%)	1	0/112 (0%)	0
Gastrointestinal disorders
Hospitalization for rectal bleeding	0/112 (0%)	0	1/112 (0.9%)	1
Nausea and vomitting	1/112 (0.9%)	1	0/112 (0%)	0
General disorders
Unsteady gait with a subsequent fall, increased confusion and tremulousness	2/112 (1.8%)	2	0/112 (0%)	0
Edema	1/112 (0.9%)	1	0/112 (0%)	0
Hepatobiliary disorders
Elevated liver enzymes	0/112 (0%)	0	1/112 (0.9%)	1
Infections and infestations
Hospitalization for Urinary Tract infection	0/112 (0%)	0	1/112 (0.9%)	1
Investigations
Increased creatine level	1/112 (0.9%)	1	0/112 (0%)	0
Metabolism and nutrition disorders
Medical complications due to alcohol abuse	0/112 (0%)	0	1/112 (0.9%)	1
Nervous system disorders
numbness	1/112 (0.9%)	1	1/112 (0.9%)	1
Psychiatric disorders
Psychiatric condition worsening	9/112 (8%)	9	11/112 (9.8%)	12
Suicide	0/112 (0%)	0	1/112 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
pulmonary edema	1/112 (0.9%)	1	0/112 (0%)	0
Medical intervention for Bronchitis	1/112 (0.9%)	1	1/112 (0.9%)	1
Skin and subcutaneous tissue disorders
Rash	1/112 (0.9%)	1	0/112 (0%)	0
Surgical and medical procedures
Back surgery	1/112 (0.9%)	1	0/112 (0%)	0
Vascular disorders
Circulatory condition	1/112 (0.9%)	1	2/112 (1.8%)	3
Low blood pressure	1/112 (0.9%)	1	0/112 (0%)	0
Other (Not Including Serious) Adverse Events
	Lithium (LI)		Divalproex (DV)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/112 (61.6%)		70/112 (62.5%)
Cardiac disorders
Cardiac change	6/112 (5.4%)	6	5/112 (4.5%)	5
Endocrine disorders
Change in Thyroid level	1/112 (0.9%)	1	0/112 (0%)	0
Eye disorders
Vision disturbance	1/112 (0.9%)	1	0/112 (0%)	0
Gastrointestinal disorders
Gastrointestinal symptoms	24/112 (21.4%)	33	26/112 (23.2%)	35
Infections and infestations
Infection	4/112 (3.6%)	6	1/112 (0.9%)	1
Injury, poisoning and procedural complications
Fall	19/112 (17%)	27	20/112 (17.9%)	27
Accidental injury	1/112 (0.9%)	1	0/112 (0%)	0
Investigations
weight gain	13/112 (11.6%)	14	23/112 (20.5%)	27
Weight loss	13/112 (11.6%)	15	6/112 (5.4%)	6
Change in pre existing high blood pressure	0/112 (0%)	0	2/112 (1.8%)	2
Change in Amylase and Lipase lab values	6/112 (5.4%)	8	0/112 (0%)	0
Increased creatine level in lab work	1/112 (0.9%)	1	0/112 (0%)	0
Nosebleed	1/112 (0.9%)	1	0/112 (0%)	0
laboratory finding Increased liver enzymes	0/112 (0%)	0	3/112 (2.7%)	3
laboratory findings increased white blood count	0/112 (0%)	0	3/112 (2.7%)	3
Metabolism and nutrition disorders
Elevated glucose	4/112 (3.6%)	8	0/112 (0%)	0
Decrease in sodium	0/112 (0%)	0	1/112 (0.9%)	1
Calcium Deficiency	1/112 (0.9%)	1	0/112 (0%)	0
Musculoskeletal and connective tissue disorders
Pain	5/112 (4.5%)	5	6/112 (5.4%)	6
Nervous system disorders
Tremor	7/112 (6.3%)	10	2/112 (1.8%)	4
Sedation	7/112 (6.3%)	7	3/112 (2.7%)	5
Decreased need for sleep	1/112 (0.9%)	1	1/112 (0.9%)	1
Memory Change	1/112 (0.9%)	1	1/112 (0.9%)	1
Headache	5/112 (4.5%)	5	3/112 (2.7%)	4
Dizziness	3/112 (2.7%)	4	1/112 (0.9%)	2
Restlessness	2/112 (1.8%)	2	1/112 (0.9%)	1
Sinus tension	1/112 (0.9%)	1	1/112 (0.9%)	1
Psychiatric disorders
Worsening psychiatric symptoms	2/112 (1.8%)	6	5/112 (4.5%)	10
Renal and urinary disorders
Elevated blood levels	0/112 (0%)	0	4/112 (3.6%)	4
Urinary dysfunction	6/112 (5.4%)	6	3/112 (2.7%)	3
Reproductive system and breast disorders
Sexual dysfunction	1/112 (0.9%)	1	1/112 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory symptoms	7/112 (6.3%)	8	6/112 (5.4%)	6
Skin and subcutaneous tissue disorders
Skin disorder	2/112 (1.8%)	2	7/112 (6.3%)	8
Vascular disorders
Hypertension	3/112 (2.7%)	5	4/112 (3.6%)	7

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.