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Trial record 1 of 1 for:    jonathan Savitz AND depression
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Lipopolysaccharide (LPS) Challenge in Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03142919
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : May 1, 2019
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 2

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.

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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: Response to Inflammatory Challenge in Major Depressive Disorder
Actual Study Start Date : September 7, 2017
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2022

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: One week ]
    The SHAPS is a 14-item self-administered questionnaire, with each item scored from 1-4 (strongly agree through strongly disagree; range 14-56), with higher scores indicating greater anticipatory, not consummatory, anhedonia. Disagreement (i.e. score of 3 or 4) on at least three items is defined as indicating clinically significant anhedonia.


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

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

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

  4. Tumor Necrosis Factor (TNF) protein levels [ Time Frame: One week ]
    Measure of systemic inflammation in pg/mL



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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) or treated with only one anti-depressant medication. 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.

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 attempt within the past 12 months.
  • Psychosis
  • 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 use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study
  • 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 or history of addiction to opioids or other analgesics
  • Current and/or past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs (does not apply where medications are taken for different purpose e.g. anti-hypertensives for migraine).
  • Evidence of recreational drug use from urine test.
  • Lifetime use of methamphetamine

Health Factors:

  • BMI > 35 because of the effects of obesity on pro-inflammatory cytokine activity
  • 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:

    1. screening supine systolic blood pressure >140 mmHg or <100 mmHg
    2. screening supine diastolic blood pressure >90 mmHg or <60 mmHg
    3. 12-lead EKG demonstrating a PR interval > 0.2 msec, QTc >450 or QRS >120 msec If the QTc exceeds 450 msec, or QRS exceeds 120 msec, the EKG will be repeated 2 more times and the median value will be used
    4. pulse less than 50 beats/minute or greater than 100 beats/minute
    5. temperature greater than 99.5F.

      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
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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
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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.
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Responsible Party: Jonathan Savitz, Assistant Professor, Laureate Institute for Brain Research, Inc.
ClinicalTrials.gov Identifier: NCT03142919    
Other Study ID Numbers: 2016-002-00
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms