Microbiome of Depression & Treatment Response to Citalopram

NCT ID: NCT02330068

Last Updated: 2018-03-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 34 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-12-31

Brief Summary

The purpose of this study is to evaluate the feasibility of developing a microbiome probe of depression and to evaluate the microbiome change in a preliminary analysis of treatment response (n=20) vs. non response (n=20) to the antidepressant citalopram. This study is a 12 week open trial that will enroll approximately 80 participants (anticipated 40 study completers with paired biomarker data) with an episode of major depression, Bipolar I or Bipolar II and 40 age- and sex-matched healthy controls.

Detailed Description

The study will be conducted at Mayo Clinic Jacksonville Department of Psychiatry (recruit up to 10 patients and 10 controls with paired data) and Mayo Clinic Depression Center in Rochester (recruit up to 30 patients and 30 controls with paired data). Patients with major depression, Bipolar Disorder I or Bipolar Disorder II confirmed by structured diagnostic interview (SCID) and moderate symptom severity (Quick Inventory of Depressive Symptomatology or S-C16) will be enrolled in the 12 week study. We will explore the gut microbiome (and its genetic material) and gut-brain markers of inflammation (cortisol, cytokines) from stool specimens and serum samples, respectively. Collections will be at baseline, week 2, and week 12 of the study. Healthy controls matched for age, sex (including menopausal status of female subjects), and body-mass index (BMI) will have only baseline stool and serum collections. Statistical t-tests will be used to assess baseline differences between patient and controls in microbiome and inflammatory markers. Treatment response (50% reduction in QIDS), treatment remission (QIDS-C16 < 6) will be analyzed with change in microbiome and inflammation markers. Correlational analysis with multiple testing corrections will be conducted between depression symptom severity and measures of cortisol, cytokines, and gut microbiome composition.

This study will focus on early translation of Dr. Fryer and Dr. Chia's research and will bring the gut-brain interface to the field of individualizing treatment to patients who struggle with depression. This project will provide insight into how gut microbiota may be implicated in depression, how antidepressant treatments alter microbiota composition, and how these factors impact key physiologic mediators of depression (i.e. cortisol and cytokine levels). The public health implications of more focused drug development and treatment for depression are substantial.

Conditions

Major Depressive Disorder, Bipolar I and Bipolar II

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Controls

Males and females ages 18-55 without Major Depressive Disorder, Bipolar I or Bipolar II who are not on an antidepressant and do not have a first degree relative with a diagnosis of Major Depressive Disorder and not currently taking citalopram.

No interventions assigned to this group

Cases

Male or female participants ages 18-55 with Major Depressive Disorder, Bipolar I or Bipolar II whom antidepressant treatment is deemed necessary will be given citalopram.

citalopram

Intervention Type: DRUG

Cases

Interventions

citalopram

Cases

Intervention Type: DRUG

Other Intervention Names

Celexa

Eligibility Criteria

Inclusion Criteria

• Outpatients or inpatients with nonpsychotic major depressive disorder (MDD) or Bipolar I or II Disorder.
• A score of >16 on the QIDS
• Outpatients or inpatients for whom antidepressant treatment is deemed appropriate by the treating clinician
• Subjects who are between 18-55 years of age

Exclusion Criteria

• Contraindications to citalopram treatment
• Axis I or II disorder other than depression that is the primary reason for seeking treatment intervention and/or psychiatric care
• Subjects diagnosed with Borderline Personality Disorder (BPD) as their primary diagnosis.
• For healthy controls, a first degree relative who has been diagnosed with an Axis I disorder
• Patients with schizophrenia, schizoaffective disorder, or bipolar I disorder
• Antidepressant treatment within 4 days of study (1 week if fluoxetine). Subjects currently on antidepressant medication with subtherapeutic results in terms of depression management after providing informed consent, will undergo a medication taper and discontinuation prior to initiation of citalopram treatment. The subject must be off of previous antidepressants for at least 4 days week prior to starting citalopram (1 week if fluoxetine). The subject will be closely monitored by the research study psychiatrist (with or without additional monitoring from primary clinical psychiatric providers). The medication taper is left up to the research study psychiatrist in consultation with patient's primary care or psychiatric provider. Study subjects who cannot be safely tapered from their medication or experience adverse effects during the taper will be excluded from the study
• Study subjects using their antidepressant medication for management of nicotine dependence, chronic pain, migraine prophylaxis, or other diagnoses will not be eligible for the study unless they remain on a stable dose of the medication for the 12 weeks of the study.
• Trazodone, melatonin, and diphenhydramine may be used as rescue medications for insomnia. Benzodiazepines may be used for treatment of anxiety, not to exceed 4 mg/24 hour of lorazepam
• Subjects who are currently on an antibiotic or an antibiotic within 2 weeks. (Topical antibiotics are OK)
• Daily use of aspirin, NSAID's or Warfarin (low dose of baby aspirin OK)
• Subjects unable to give informed consent are excluded
• Pregnant subjects will be excluded
• Subjects who are currently breastfeeding and who plan to continue breastfeeding will be excluded
• Postmenopausal women are not eligible for this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

William V. Bobo, M.D.

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Bobo, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

14-002154

Identifier Type: -

Identifier Source: org_study_id