Clinical trial NCT03142919: Lipopolysaccharide (LPS) Challenge in Depression
Official title: Response to Inflammatory Challenge in Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Mood Disorder
MDD
Endotoxin
MRI
CRP
Lead sponsor: Laureate Institute for Brain Research, Inc.
Sponsor class: OTHER
First posted: 2017-05-08
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: LPS Challenge in Individuals with Major Depressive Disorder

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.

Eligibility 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.

Primary outcomes:
measure: Change in Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Baseline, 1 hour, 2-hours, 3-hours, 4-hours, 6 hours, 24 hours, one week
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline, 6 hours, 24 hours, one week
measure: Change in Interleukin 6 (IL-6) protein levels
timeFrame: Baseline, 1 hour, 2-hours, 3-hours, 6 hours, 24 hours, one week
measure: Change in Interleukin 10 (IL-10) protein levels
timeFrame: Baseline, 1 hour, 2-hours, 3-hours, 6 hours, 24 hours, one week
measure: Change in Tumor Necrosis Factor (TNF) protein levels
timeFrame: Baseline, 1 hour, 2-hours, 3-hours, 6 hours, 24 hours, one week
measure: Change in Blood Oxygenation Level Dependent signal (BOLD) Ventral Striatum
timeFrame: Baseline line; 2-3 hours
measure: Change in Blood Oxygenation Level Dependent signal (BOLD) Insula
timeFrame: Baseline line; 2-3 hours
measure: Change in Temperature
timeFrame: Baseline, 1 hour, 2-hours, 3-hours, 4-hours, 6 hours, 24 hours, one week
Other outcomes:
Locations:
city: Tulsa
country: United States
facility: Laureate Institute for Brain Research
state: Oklahoma
Study officials:
References: