Characterization of Microbial, Immune and Epigenetic Biomarkers for Major Depressive Disorder and ECT Treatment

October 11, 2018 updated by: Ziv Hospital
The investigators aim to characterize fecal microbial biomarkers as well as blood cytokine levels in MDD patients vs. healthy controls. 40 MDD patients will be recruited for this study, as well as 20 healthy age-matched participants (as a control group). Following signing of informed consent, stool and blood (20 ml) samples will be collected from all participants, for microbial composition assessment, and blood measures of inflammation and protein expression. According to clinical assessment of the diagnosed MDD patients, the psychiatrist will recommend SSRI or ECT treatment, and the patients will be divided accordingly to treatment group. Clinical status will be assessed by the Hamilton Depression Rating Scale (HAM-D) scored by a psychiatrist at the starting point (before treatment), after 4 weeks of treatment (as ECT-group patients receive 8-12 treatments on average). A lowering in the HAM-D score will be considered clinical improvement which may be attributed to treatment. The investigators expect a treatment success rate of over 50% for ECT according to past experience. Blood and stool samples will be collected from MDD patients after 4 weeks of treatment, repeating inflammatory, protein expression and microbial measurements and comparing them to initial results. Additional data recorded will include age, BMI, ethnicity, previous medication use, and number of ECT treatments or current medication.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

All procedures will be approved by the ZIV Helsinki ethics committee. Recruitment and clinical assessment: 40 MDD patients will be recruited for this study, as well as 20 healthy age-matched participants (as a control group). A psychiatrist not involved in the study will assess the qualification of the patients for signing informed consent. Following signing of informed consent, stool and blood (20 ml) samples will be collected from all participants, for microbial composition assessment, and blood measures of inflammation and protein expression. According to clinical assessment of the diagnosed MDD patients, the psychiatrist will recommend SSRI or ECT treatment, and the patients will be divided accordingly to treatment group. Clinical status will be assessed by the Hamilton Depression Rating Scale (HAM-D) scored by a psychiatrist at the starting point (before treatment), after 4 weeks of treatment (as ECT-group patients receive 8-12 treatments on average). A lowering in the HAM-D score will be considered clinical improvement which may be attributed to treatment. The investigators expect a treatment success rate of over 50% for ECT according to our past experience. The investigators will collect blood and stool samples from MDD patients after 4 weeks of treatment, repeat inflammatory, protein expression and microbial measurements and compare them to initial results. Additional data recorded will include age, BMI, ethnicity, previous medication use, and number of ECT treatments or current medication.

Inclusion criteria: MDD patients with stable depression clinically diagnosed by a psychiatrist according to the Hamilton Depression Scale. Patient age may range between 18-80 years, as depression is more common in older people as represented by a median age of over 55 in the treated population at the Ziv Medical Center.

Exclusion criteria: Patients receiving antibiotics in the past 3 months prior to sampling, patients suffering from chronic gastrointestinal diseases or other chronic diseases such as autoimmune or cancer, patients with comorbidities such as schizophrenia.

Blood samples: Whole blood will be centrifuged and serum samples will be kept at -80C until analysis for inflammatory measurements. Additionally, lymphocytes will be purified, RNA will be extracted and qRT-PCR will be performed to test immune protein and receptor expression (IL-1β, IL-1R1, IL-6, TNF-α, TNF1, TNF2) as well as additional proteins related to MDD (e.g. cannabinoid receptor 1- CNR1, CD38, oxytocin receptor- OXTR, brain-derived neurotrophic factor - BDNF).

Inflammatory measures in the serum: We will measure levels of pro and anti-inflammatory cytokines by multiplex tests including IL-1, IL-6, IL-8, IL-10, and TNFα using a Bio-Plex kit (Bio-Rad). The assay plate will be read on a MAGPIX multiplex reader (Bio-Rad).

Stool samples: stool samples will be stored within 4 hours from collection at -80C until processing.

Microbial analysis: Microbial DNA will be purified from stool and a barcoded 16S rRNA library from each subject will be generated from which we will obtain ~300,000 reads per sample using the Illumina MiSeq platform (NGS sequencing) at the Faculty of Medicine, Bar Ilan University. Sequences will be analyzed by QIIME. Additionally, microbial RNA will be extracted from stool in order to test microbial gene expression via metatranscriptomics (NGS sequencing).

Statistical analysis: All assays will be conducted using statistical software SPSS version 24 (SPSS Inc., Chicago, IL, USA).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

40 MDD patients will be recruited for this study, as well as 20 healthy age-matched participants (as a control group).

Description

Inclusion Criteria:

  • Healthy controls
  • MDD patients with stable depression clinically diagnosed by a psychiatrist according to the *Hamilton Depression Scale.
  • Ages 18-80

Exclusion Criteria:

  • Patients receiving antibiotics in the past 3 months prior to sampling
  • Patients suffering from chronic gastrointestinal diseases
  • Patients with chronic diseases such as autoimmune or cancer
  • Patients with psychiatric co-morbidities such as schizophrenia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Control
Healthy controls
Diagnostic test: Fecal microbiota composition analysis and blood cytokine level analysis
Fecal microbiota composition analysis and blood cytokine level analysis
ECT
MDD patients receiving ECT treatment
Diagnostic test: Fecal microbiota composition analysis and blood cytokine level analysis
Fecal microbiota composition analysis and blood cytokine level analysis
SSRI
MDD patients receiving SSRI treatment
Diagnostic test: Fecal microbiota composition analysis and blood cytokine level analysis
Fecal microbiota composition analysis and blood cytokine level analysis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Correlation between MDD and fecal microbial communities (as determined by NGS sequencing) and as well as immune components (cytokine levels in blood)
Time Frame: 4 week followup
4 week followup
Correlation between ECT treatment and fecal microbial communities (as determined by NGS) as well as blood cytokines in MDD patients
Time Frame: 4 week followup
4 week followup
Correlation between SSRI treatment and fecal microbial communities (as determined by NGS) as well as blood cytokines in MDD patients
Time Frame: 4 week followup
4 week followup

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ziv Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2019

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 16, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0069-18-ZIV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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