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Lipopolysaccharide (LPS) Challenge in Depression

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ClinicalTrials.gov Identifier: NCT03142919
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Jonathan Savitz, Laureate Institute for Brain Research, Inc.

Brief Summary:
LPS Challenge in Individuals with Major Depressive Disorder

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Biological: Lipopolysaccharide Biological: Placebo Phase 1

Detailed Description:
The aim of this project is to understand the biological differences between two distinct subtypes of depression, patients with and without inflammation as defined by c-reactive protein (CRP). Using a double-blinded, parallel group, placebo-controlled design, participants will be phenotyped before and after a low-dose lipopolysaccharide (LPS) challenge designed to perturb the immune system and trigger a transient, mild inflammatory response. This experimental design will allow for the delineation of the homeostatic mechanisms underlying sensitivity to inflammation-related depression. Low-dose LPS has been used by multiple groups to safely induce transient inflammatory responses in humans. The pilot study is expected to take approximately one year to complete.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Lipopolysaccharide (LPS) Challenge in Depression
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High CRP LPS Intervention
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Biological: Lipopolysaccharide
Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
Other Name: Endotoxin, CCRE

Active Comparator: Low CRP LPS Intervention
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Biological: Lipopolysaccharide
Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
Other Name: Endotoxin, CCRE

Placebo Comparator: High CRP LPS Placebo
High CRP Individuals with Major Depressive Disorder receiving placebo
Biological: Placebo
Saline solution
Other Name: Saline solution

Placebo Comparator: Low CRP LPS Placebo
Low CRP Individuals with Major Depressive Disorder receiving placebo
Biological: Placebo
Saline solution
Other Name: Saline solution




Primary Outcome Measures :
  1. Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: Day 1 ]
    measure of anhedonia


Secondary Outcome Measures :
  1. Interleukin 6 (IL-6) protein levels [ Time Frame: Day 1 ]
    pro-inflammatory cytokine measured in pg/mL

  2. Blood Oxygenation Level Dependent signal (BOLD) Ventral Striatum [ Time Frame: Day 1 ]
    beta-weights for the average activity across the ventral striatum

  3. Blood Oxygenation Level Dependent signal (BOLD) Insula [ Time Frame: Day 1 ]
    beta-weights for the average activity across the insula

  4. Methylation of Interleukin 6 (IL-6) gene [ Time Frame: Day 1 ]
    Methylation of IL-6 gene measured as % of methylated CpGs

  5. Methylation of Tumor Necrosis Factor (TNF) gene [ Time Frame: Day 1 ]
    Methylation of TNF gene measured as % of methylated CpGs

  6. Tumor Necrosis Factor (TNF) protein levels [ Time Frame: Day 1 ]
    measure of systemic inflammation in pg/mL



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Both healthy controls and depressed participants will be required to be in good general health (as evaluated during Visit 1, including EKG) and to be 18-55 years of age. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and be unmedicated for at least 3 weeks (8 weeks for fluoxetine). Half the depressed participants (N=50) will be required to have a high-sensitivity C-Reactive Protein (CRP) score of ≥3 mg/L, and half the participants will be required to have a CRP score of ≤1 mg/L.

Exclusion Criteria:

General Exclusion Criteria:

  • Pregnancy
  • Previous history of fainting during blood draws.

Medical Conditions:

  • A history of a head injury with loss of consciousness.
  • Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders.
  • Presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders.
  • Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk.
  • Presence of chronic infection that may elevate pro-inflammatory cytokines.
  • Presence of an acute infectious illness or receipt of a vaccination in the two weeks prior to an experimental session.

Psychiatric Disorders:

  • Current severe suicidal ideation or lifetime history of a suicide attempt
  • Bipolar disorder
  • Substance abuse or dependence within the previous 6 months
  • Age of onset of depression >40 years.

Contraindications for MRI:

  • Severe claustrophobia
  • Bodily implants of unsafe paramagnetic materials such as pace-makers and aneurysm clips.

Medications:

  • Current and/or past regular use of hormone-containing medications (excluding contraceptives)
  • Current regular use of non-steroid anti-inflammatory drugs
  • Current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists
  • Current use of analgesics such as opioids
  • Current use of cardiovascular medications, including antihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs.
  • Evidence of recreational drug use from urine test.

Health Factors:

  • BMI > 35
  • Clinically significant abnormalities on screening laboratory tests
  • Abnormal EKG
  • In addition, participants who on arrival to the study, show any of the following symptoms will not be allowed to complete the study: (a) blood pressure less than 90/60 or greater than 140/100, (b) pulse less than 50 beats/minute or greater than 100 beats/minute, and (c) temperature greater than 99.5°F.

Non-English speaking participants:

  • The majority of the assessments proposed for this study have not been translated from English, thus, non-English speaking volunteers will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03142919


Contacts
Contact: Jonathan Savitz, Ph.D. 918-502-5104 jsavitz@laureateinstitute.org
Contact: Nour El-Sabbagh, B.A. 918-502-5126 Nel-Sabbagh@laureateinstiute.org

Locations
United States, Oklahoma
Laureate Institute for Brain Research Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Nour El-Sabbagh, B.A.    918-502-5126    nel-sabbagh@laureateinstitute.org   
Sponsors and Collaborators
Laureate Institute for Brain Research, Inc.

Responsible Party: Jonathan Savitz, Assistant Professor, Laureate Institute for Brain Research, Inc.
ClinicalTrials.gov Identifier: NCT03142919     History of Changes
Other Study ID Numbers: 2016-002-00
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jonathan Savitz, Laureate Institute for Brain Research, Inc.:
Mood Disorder
MDD
Endotoxin
MRI
CRP

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders