Gao Bipolar Spectrum Lithium/Quetiapine Study

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01526148
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This is a 4-month randomized open-label comparative safety, tolerability, and effectiveness trial of Lithium versus Quetiapine for subjects presenting in any phase of Bipolar who currently require a medication change for their illness. Stratified randomization will reduce bipolar type I , bipolar type II , or sub-threshold imbalance across cells. The enrollment goal is 60 subjects, over 24 months from initial regulatory approval. The primary outcome is the difference between lithium and quetiapine in the time to 'all cause' medication discontinuation.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Lithium; Drug: Quetiapine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparative Safety, Tolerability, and Effectiveness of Lithium Versus Quetiapine in Patients Across the Spectrum of Bipolar Disorder
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lithium	Drug: Lithium; Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.; Other Names: Lithium Carbonate Eskalith
Active Comparator: Quetiapine	Drug: Quetiapine; Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.; Other Names: Seroquel

Outcome Measures

Primary Outcome Measures

1. Time to Study Discontinuation [Week 16]

   The time, as measured in number of days, for discontinuation due to all causes will be measured and used as the primary outcome measure

Secondary Outcome Measures

1. Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [Screening and Week 16]

   Change in homeostatic model assessment for insulin resistance (HOMA-IR) from screening to end of study. Insulin resistance is a condition in which cells fail to respond to the normal actions of the hormone in the body. The HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. The higher the score, the higher the level of insulin resistance.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to provide informed consent before beginning any study-specific procedures

• Male and female patients at least 18 years of age

• Meets Diagnostic and Statistical Manual -IV criteria for BPI, BP II, or National Comorbidity Survey-R criteria for sub-threshold BP with or without symptoms, in need of medication adjustment(s)

• Willing to be randomized to either Lithium or Quetiapine

• If a sexually active female of childbearing potential, be using a reliable method of contraception, such as oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods (e.g. condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, and tubal ligation

• Women with reproductive potential must have a negative urine pregnancy test

Exclusion Criteria:

• Unwilling to comply with study requirements

• Patients who have had severe adverse reaction to Lithium or Quetiapine

• Patients who require inpatient care

• Drug/alcohol dependence requiring immediate acute detoxification

• Pregnancy as determined by serum pregnancy test or breastfeeding

• History of nonresponse to Lithium at doses >900 mg ≥8 wks or to Quetiapine at doses of at least 300 mg/d ≥ 8 week for depression and at least 400-600 mg/d ≥ 4 wks for mania.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Cleveland Medical Center - Mood Disorders Program	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center

Investigators

• Principal Investigator: Keming Gao, MD, PhD, University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Keming Gao, Director, Mood & Anxiety Clinic, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT01526148
• Other Study ID Numbers: 09-11-01
• First Posted: Feb 3, 2012
• Last Update Posted: Aug 16, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Bipolar Disorder; Quetiapine Fumarate; Lithium Carbonate

Study Results

Participant Flow

Arm/Group Title	Lithium	Quetiapine
Arm/Group Description	Lithium: Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.	Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.
Period Title: Overall Study
STARTED	18	24
COMPLETED	4	11
NOT COMPLETED	14	13

Baseline Characteristics

Arm/Group Title	Lithium	Quetiapine	Total
Arm/Group Description	Lithium: Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.	Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.	Total of all reporting groups
Overall Participants	18	24	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.26 (16.66)	35.58 (12.64)	38.98 (14.88)
Sex: Female, Male (Count of Participants)
Female	11 61.1%	10 41.7%	21 50%
Male	7 38.9%	14 58.3%	21 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.6%	0 0%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 38.9%	15 62.5%	22 52.4%
White	10 55.6%	9 37.5%	19 45.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Diagnosis (participants) [Number]
Bipolar I Disorder	10 55.6%	15 62.5%	25 59.5%
Bipolar II Disorder	9 50%	7 29.2%	16 38.1%
Bipolar NOS	0 0%	2 8.3%	2 4.8%

Outcome Measures

1. Primary Outcome

Title	Time to Study Discontinuation
Description	The time, as measured in number of days, for discontinuation due to all causes will be measured and used as the primary outcome measure
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium	Quetiapine
Arm/Group Description	Lithium: Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.	Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.
Measure Participants	18	24
Mean (95% Confidence Interval) [days]	41	77

2. Secondary Outcome

Title	Lithium vs. Quetiapine Effects on General Cardiovascular Disease Risk as Measured by Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Description	Change in homeostatic model assessment for insulin resistance (HOMA-IR) from screening to end of study. Insulin resistance is a condition in which cells fail to respond to the normal actions of the hormone in the body. The HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. The higher the score, the higher the level of insulin resistance.
Time Frame	Screening and Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium	Quetiapine
Arm/Group Description	Lithium: Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.	Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.
Measure Participants	18	24
Mean (Standard Deviation) [IR Score]	-5.5 (15.9)	0.2 (1.6)

Adverse Events

Arm/Group Title	Lithium		Quetiapine
Arm/Group Description	Lithium: Lithium will be initiated at 300 mg per day and titrated in 300 mg increments every 7days as tolerated with blood lithium levels > 0.6mEq/L.		Quetiapine: Quetiapine will be started at 50 mg per day at bedtime and titrated up to 300 mg as tolerated over 1 week.
All Cause Mortality
	Lithium		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lithium		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Lithium		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/18 (88.9%)		21/24 (87.5%)
Gastrointestinal disorders
Stomach Upset	5/18 (27.8%)	5	0/24 (0%)	0
Nausea	4/18 (22.2%)	4	0/24 (0%)	0
Vomiting	1/18 (5.6%)	1	0/24 (0%)	0
Consitpation	0/18 (0%)	0	3/24 (12.5%)	3
General disorders
Excessive sleepiness / daytime somnolence	7/18 (38.9%)	7	12/24 (50%)	12
Increased thirst	4/18 (22.2%)	4	4/24 (16.7%)	4
Insomnia	3/18 (16.7%)	3	0/24 (0%)	0
Headache	2/18 (11.1%)	2	2/24 (8.3%)	2
Muscle Stiffness	1/18 (5.6%)	1	1/24 (4.2%)	1
Cognitive Impairment	1/18 (5.6%)	1	3/24 (12.5%)	3
Unusual discomfort to warm temperatures	1/18 (5.6%)	1	0/24 (0%)	0
Increased Appetite	1/18 (5.6%)	1	2/24 (8.3%)	2
Weight Gain	1/18 (5.6%)	1	1/24 (4.2%)	1
Dizziness/Lightheadedness	1/18 (5.6%)	1	6/24 (25%)	6
Dry Mouth	0/18 (0%)	0	11/24 (45.8%)	11
Hot flashes	0/18 (0%)	0	2/24 (8.3%)	2
Nervous system disorders
Tremor	2/18 (11.1%)	2	3/24 (12.5%)	3
Psychiatric disorders
Irritability	0/18 (0%)	0	2/24 (8.3%)	2
Renal and urinary disorders
Increased urination	2/18 (11.1%)	2	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

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.