Ceftriaxone in the Management of Bipolar Depression

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00566111
• Collaborator: Stanley Medical Research Institute (Other)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

We aim to study the efficacy of intravenous ceftriaxone in a four-week, inpatient, placebo-controlled, double-blind study, as an augmentation therapy in patients with bipolar disorder, currently depressed, who have failed to respond to conventional treatments.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Depression	Drug: ceftriaxone; Drug: Saline solution	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Modulation of Glutamatergic Neurotransmission in the Treatment of Bipolar Depression
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A	Drug: ceftriaxone; 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.; Other Names: Rocephin Ceftriaxone Sodium
Placebo Comparator: P	Drug: Saline solution; Saline solution will be administered IV via midline, 7 days a week for 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline. [4 weeks]

   Number of patients with scores that decreased at four weeks.

Secondary Outcome Measures

1. Change in Score on the 16-item Quick Inventory of Depressive Symptoms (QIDS) From Baseline. [4 weeks]

   Number of patients with scores that decreased at four weeks.

2. Number of Subjects Who Achieve Remission as Defined by a HDRS Score < 7. [4 weeks]

3. Change in Montgomery Asberg Depression Rating Scale (MADRS)Score From Baseline. [4 weeks]

   The number of patients that had a decrease on MADRS at 4 weeks.

4. Change in Ratings on the Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP). [4 weeks]

   The number of patients that had a decrease on CGI-BP at 4 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• DSM-IV diagnosis of bipolar disorder

• Presence of a current major depressive episode on the SCID

• Score of 17 or greater on the HDRS

• Failure to respond to two previous medication trials

• Capable of giving voluntary written consent

Exclusion Criteria:

• Hypersensitivity to penicillin or cephalosporin, resulting in anaphylaxis

• Significant current substance dependence/abuse within 3 months preceding the trial

• Significant history of intravenous drug abuse

• Active suicidal ideation

• Pregnant/lactating mothers

• Significant medical history

• Patients on anticoagulation treatment

• Patients who test positive for HIV or Hep B or C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University
• Stanley Medical Research Institute

Investigators

• Principal Investigator: Zubin Bhagwagar, MD PhD, Yale University
• Principal Investigator: Gerard Sanacora, MD PhD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Mineur YS, Picciotto MR, Sanacora G. Antidepressant-like effects of ceftriaxone in male C57BL/6J mice. Biol Psychiatry. 2007 Jan 15;61(2):250-2. Epub 2006 Jul 24.
• Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005 Jan 6;433(7021):73-7.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00566111
• Other Study ID Numbers: 0704002567
• First Posted: Dec 3, 2007
• Last Update Posted: Mar 31, 2020
• Last Verified: Aug 1, 2016

• Keywords provided by Yale University: Ceftriaxone; Acute Antidepressant Effects; Glutamatergic System; Double-Blind; Mood Disorders; Bipolar Disorder; Depression; Affective Disorders
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Ceftriaxone

Study Results

Participant Flow

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	1
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Ceftriaxone	Placebo	Total
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	1 33.3%	2 40%
Male	1 50%	2 66.7%	3 60%

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline.
Description	Number of patients with scores that decreased at four weeks.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

only participants with complete data at 4 weeks were analyzed

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Measure Participants	2	1
Number [participants]	2 100%	1 33.3%

2. Secondary Outcome

Title	Change in Score on the 16-item Quick Inventory of Depressive Symptoms (QIDS) From Baseline.
Description	Number of patients with scores that decreased at four weeks.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

These data were not collected.

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Subjects Who Achieve Remission as Defined by a HDRS Score < 7.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

only participants with complete data at 4 weeks were analyzed

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Measure Participants	2	1
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	Change in Montgomery Asberg Depression Rating Scale (MADRS)Score From Baseline.
Description	The number of patients that had a decrease on MADRS at 4 weeks.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

only participants with complete data at 4 weeks were analyzed

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Measure Participants	2	1
Number [participants]	2 100%	0 0%

5. Secondary Outcome

Title	Change in Ratings on the Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP).
Description	The number of patients that had a decrease on CGI-BP at 4 weeks.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

only patients with complete data at 4 weeks were analyzed

Arm/Group Title	Ceftriaxone	Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.	Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
Measure Participants	2	1
Number [participants]	2 100%	1 33.3%

Adverse Events

Time Frame	Up to 4 weeks.
Arm/Group Title	Ceftriaxone		Placebo
Arm/Group Description	ceftriaxone: 2g per day which will be administered IV via midline, 7 days a week for 4 weeks.		Saline solution: Saline solution will be administered IV via midline, 7 days a week for 4 weeks.
All Cause Mortality
	Ceftriaxone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ceftriaxone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Ceftriaxone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		2/3 (66.7%)
Gastrointestinal disorders
Diarrhea	0/2 (0%)	0	1/3 (33.3%)	1
General disorders
Drowsiness	1/2 (50%)	1	1/3 (33.3%)	1
Difficulty Concentrating	2/2 (100%)	2	2/3 (66.7%)	2
Dry Mouth	1/2 (50%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Poor Coordination	0/2 (0%)	0	1/3 (33.3%)	1
Nervous system disorders
Tremors	1/2 (50%)	1	0/3 (0%)	0
Psychiatric disorders
Nightmares	1/2 (50%)	1	0/3 (0%)	0

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.