Depression, Obesity and Inflammatory Markers

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02765100
• Collaborator: Weill Cornell Medical College in Qatar (Other)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 60
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to better understand the relationship between bipolar disorder, body weight, and inflammation in the body (N=180). People with bipolar depression (N = 50)will be offered a place in a pilot study looking to see if the antibiotic minocycline added to current psychiatric medications has an effect on mood. A separate consent form will be provided for the pilot study. Numerous studies have documented the presence of altered immune function and elevation of inflammatory markers in patients with depression. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system. While a small number of studies have found elevated inflammatory markers in bipolar mania, very little has been reported about inflammation in bipolar depression, and none of these studies have addressed the relationship of inflammatory markers with obesity in bipolar disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Depression; Obesity	Drug: Minocycline	N/A

Detailed Description

Aim 1 (N=180)will examine relationships between the levels of the inflammatory markers and current clinical state (depressed, manic or euthymic) with the hypothesis that Inflammatory markers will be higher in depression and mania relative to the euthymic state.

Aim 2 (N=180)will examine relationships between inflammatory markers and BMI in bipolar patients with the hypothesis that inflammatory markers will correlate positively with BMI.

Aim 3 (N=180)will examine the relationship between depression, obesity and inflammatory markers with the hypothesis that depressed (or manic) bipolar patients who are also obese will have higher inflammatory markers than either obese euthymic patients or non-obese depressed or manic patients.

Aim 4. (N=50) The pilot study will be to conduct a proof of concept add-on treatment study of the antibiotic minocycline for bipolar patients who are depressed, likely to be obese and likely to have elevated inflammatory markers and increased risk of heart disease. This is a proposal to conduct a 2-site trial of 50 subjects to examine the value of minocycline augmentation in bipolar depressed patients who are incompletely responsive to initial treatment with anti depressants and/or mood stabilizers. The investigators will compare two subgroups of depressed patients, those who have high (N=25) versus those who have low (N=25) levels of C-reactive protein (CRP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Depression, Obesity and Inflammatory Markers
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Oct 1, 2019
• Actual Study Completion Date: Oct 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low CRP Subjects have CRP > 3	Drug: Minocycline; Minocycline 100 mg twice a day; Other Names: Minocin
Experimental: High CRP Subjects have CRP =/> 3	Drug: Minocycline; Minocycline 100 mg twice a day; Other Names: Minocin

Outcome Measures

Primary Outcome Measures

1. Change in Depression as Measured by the Hamilton Depression Scale Collected at Baseline and Week 8 [Baseline; week 8]

   Scale ranges from 0-52. Greater change means greater improvement of depression from baseline to week 8.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with Bipolar Disorder and current depressive symptoms

• Hamilton Depression Scale score > 18

• Failed an adequate trial of at least one antidepressant or mood stabilizer of at least 4 weeks duration. Medication history will be recorded using the Antidepressant Treatment History Form

• 18 years or older

• Fluent in English or Arabic

• Have the capacity to understand the nature of the study and sign the written informed consent.

Exclusion Criteria:

• A current diagnosis of Schizophrenia or other psychotic disorder, or Dementia Alzheimer Type or related cognitive disorders.

• Principal diagnosis of Post-Traumatic Stress Disorder, Anorexia or Bulimia Nervosa, Obsessive-Compulsive Disorder. We define principal as the most pressing clinical problem.

• Pregnant or nursing

• Axis II diagnosis of antisocial, schizotypal or severe borderline personality disorder (defined as patients who are high risk for being unable to complete the study due to hospitalization, suicide attempts, significant self-mutilation, or other self-injurious or destructive behavior).

• Patients who currently meet criteria for Alcohol or other Substance-Related Dependence Disorder (with the exception of nicotine dependence) who require detoxification.

• Patients who are unable to read and write English or Arabic.

• Patients having serious, unstable or terminal medical or neurologic illness that would compromise study participation (i.e., metastatic or advanced malignancy, chronic renal failure requiring dialysis, recent myocardial infarction or unstable angina, or "end stage" chronic obstructive pulmonary disease). People with common conditions such as hypertension, insulin dependent diabetes mellitus, asthma, compensated congestive heart failure, a malignancy in remission, treated hypothyroidism, or epilepsy will not be excluded from participation.

• Autoimmune disease or chronic inflammatory diseases such as psoriasis or Crohn's disease

• Chronic infection such as hepatitis B or C or HIV

• Elevated antinuclear antibody or rheumatoid factor

• Oral glucocorticoids in the past 6 months

• Methotrexate or NSAID use in the past two weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University
• Weill Cornell Medical College in Qatar

Investigators

• Principal Investigator: James H Kocsis, MD, Weill CMC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2016

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT02765100
• Other Study ID Numbers: 1406015184
• First Posted: May 6, 2016
• Last Update Posted: Jul 1, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Weill Medical College of Cornell University: Bipolar Disorder; Obesity; Depression
• Additional relevant MeSH terms: Obesity; Depression; Depressive Disorder; Bipolar Disorder; Minocycline

Study Results

Participant Flow

Arm/Group Title	Low CRP	High CRP
Arm/Group Description	patients with a baseline C-ReactiveProtein value =/< 3 treated with minocycline 200 mg/d	patients with a baseline C-ReactiveProtein value >3 treated with minocycline 200 mg/d
Period Title: Overall Study
STARTED	9	12
COMPLETED	8	10
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Low CRP	High CRP	Total
Arm/Group Description	CRP =/< 3	CRP > 3	Total of all reporting groups
Overall Participants	9	12	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.3 (7.5)	44.5 (14.0)	48.3 (12.3)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	9 75%	11 52.4%
Male	7 77.8%	3 25%	10 47.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	8 88.9%	11 91.7%	19 90.5%
Qatar	1 11.1%	1 8.3%	2 9.5%
Hamilton Depression Scale (HAMD) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	24.8 (6.5)	23.0 (4.1)	23.8 (5.2)

Outcome Measures

1. Primary Outcome

Title	Change in Depression as Measured by the Hamilton Depression Scale Collected at Baseline and Week 8
Description	Scale ranges from 0-52. Greater change means greater improvement of depression from baseline to week 8.
Time Frame	Baseline; week 8

Outcome Measure Data

Analysis Population Description

Three participants not analyzed due to withdrawal from study

Arm/Group Title	Low CRP	High CRP
Arm/Group Description	patients with baseline CRP =/< 3	patients with baseline CRP > 3
Measure Participants	8	10
Mean (Standard Deviation) [units on a scale]	-12.2 (3.4)	-12.0 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low CRP, High CRP
	Comments	This is a pilot proof of concept study and does not require formal sample size calculations. High and low CRP groups will be compared on demographic, clinical and biological variables using two-sample t-tests or analysis of variance (ANOVA) tests for continuous variables (for nonparametric continuous variables, either Mann-Whitney tests or Kruskal-Wallis tests will be used) and chi-square tests or Fisher's exact tests for categorical variables.
	Type of Statistical Test	Equivalence
	Comments	Unless specified otherwise, each of the statistical tests above will use a two-tailed alpha-level of 0.05.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 3.4
	Estimation Comments

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	Three participants not evaluated due to early withdrawal from the study
Arm/Group Title	Low CRP		High CRP
Arm/Group Description	CRP =/< 3		CRP > 3
All Cause Mortality
	Low CRP		High CRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Serious Adverse Events
	Low CRP		High CRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Low CRP		High CRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (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.