NCT04751331 · Laureate Institute for Brain Research, Inc.
Neural Response to Inflammatory Challenge in Major Depressive Disorder
What this study is about
This is a parallel group, double-blinded, compared against an inactive treatment study. Participants with MDD (n=90) and HC (n=90) will be randomly assigned (2:1) to receive either lipopolysaccharide (LPS) (0.8ng/kg of body weight) or placebo (same volume of 0.9% saline) administered as an given through a vein (IV) bolus.
View original scientific description
This is a parallel group, double-blinded, placebo-controlled study. Participants with MDD (n=90) and HC (n=90) will be randomly assigned (2:1) to receive either lipopolysaccharide (LPS) (0.8ng/kg of body weight) or placebo (same volume of 0.9% saline) administered as an intravenous bolus. This will yield the following groups: MDD-LPS (n=60), MDD-Placebo (n=30), HC-LPS (n=60), HC-placebo (n=30). There are three main aims: to identify immune pathways and neural circuits that respond differently to LPS in MDD vs. HC subjects; (2) to test whether the strength of inflammatory changes induced by LPS is associated with degree of change in anhedonic symptoms and neural circuits in the MDD group, and (3) to identify a biotype of MDD that shows a differential immunological and neurophysiological response to LPS. The main outcome variables are symptoms of anhedonia measured with the Snaith-Hamilton Pleasure Scale (SHAPS), cytokines (Il-6, IL-8, IL-10, and TNF), and BOLD signal change in the neural circuitry mediating interoceptive processing, i.e. the insula and cingulate cortex. The exploratory aim is to determine whether the acute inflammatory response to LPS can predict the clinical course of depression over a period of six months. The main outcome of this component of the study is self-reported depressive symptoms assessed with the QIDS-SR.
Interventions
BIOLOGICAL
LPS
Lipopolysaccharide (LPS) (0.8ng/kg of body weight; E. coli group O:113)
BIOLOGICAL
Saline
0.9% saline administered as an intravenous bolus
Primary outcome measures
Inflammatory response
Time frame: 1.5 hours post infusion
Serum interleukin 6 (IL-6) (pg/mL)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 18-65 years of age. A DSM-V diagnosis of MDD will be made with the MINI International Neuropsychiatric Interview and current symptoms of depression will be measured with the clinician-administered MADRS and the self-report PHQ-9. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and/or a MADRS score of ≥7.
Exclusion criteria
- General Exclusion Criteria:
- A history of fainting during blood draws will be evaluated by the clinical team and may be deemed exclusionary. Medical Conditions:
- Moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits.
- 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.
- Bipolar disorder
- Substance abuse or dependence within the previous 6 months Contraindications for MRI:
- Cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.
- Claustrophobia that is severe enough to preclude MRI scanning. Medications:
- Current and/or past regular use of hormone-containing medications (excluding contraceptives)
- Use of medications such as oral corticosteroids which may have immunosuppressive effects.
- Current use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study (e.g. \> 3 days/week)
- 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).
- Chronic use of antibiotics such as isotretinoin or minocycline because of their potential effects on the microbiome and immune function.
- Evidence of recreational drug use from urine test.
- Lifetime use of methamphetamine
- 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:
- screening supine systolic blood pressure \>140 mmHg or \<100 mmHg
- screening supine diastolic blood pressure \>90 mmHg or \<60 mmHg
- 12-lead EKG demonstrating a PR interval \> 0.2 msec QTc \>450 or QRS \>120 msec (Bazett) 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
- pulse less than 50 beats/minute or greater than 100 beats/minute
- temperature greater than 99.5 degrees 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.
Where
- Tulsa, Oklahoma
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 21, 2026 · Source of record for eligibility and locations