Major Depressive DisorderPhase 1NCT03142919
Lipopolysaccharide (LPS) Challenge in Depression
A Phase 1 study testing Lipopolysaccharide in people with Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
Trial summary
LPS Challenge in Individuals with Major Depressive Disorder Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Lipopolysaccharide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2017to 1 Dec 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 40Show fewer
- 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:
- 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 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 99.5F.
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74136
About this study
Official title: Response to Inflammatory Challenge in Major Depressive Disorder
LPS Challenge in Individuals with Major Depressive Disorder
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Lipopolysaccharide, Placebo
- Keywords
- Mood Disorder, MDD, Endotoxin, MRI, CRP
- Medical subject headings
- Depressive Disorder, Major, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LipopolysaccharideBiological
Also called Endotoxin, CCRE
Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
PlaceboBiological
Also called Saline solution
Saline solution
| Study group | Role | What they receive |
|---|---|---|
| High CRP LPS Intervention | Experimental | High CRP Individuals with Major Depressive Disorder receiving LPS intervention Receives: Biological: Lipopolysaccharide |
| Low CRP LPS Intervention | Active comparator | Low CRP Individuals with Major Depressive Disorder receiving LPS intervention Receives: Biological: Lipopolysaccharide |
| High CRP LPS Placebo | Placebo comparator | High CRP Individuals with Major Depressive Disorder receiving placebo Receives: Biological: Placebo |
| Low CRP LPS Placebo | Placebo comparator | Low CRP Individuals with Major Depressive Disorder receiving placebo Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
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.
Measured: 2-hours
Secondary outcomes (7)
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Clinician-administered depression rating scale with scores ranging from 0-60. Higher scores indicate more depression.
Measured: 24 hours
Change in Interleukin 6 (IL-6) Protein Levels
pro-inflammatory cytokine measured in pg/mL
Measured: 2-hours
Change in Interleukin 10 (IL-10) Protein Levels
Measure of systemic inflammation in pg/mL
Measured: 2-hours
Change in Tumor Necrosis Factor (TNF) Protein Levels
Measure of systemic inflammation in pg/mL
Measured: 2-hours
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Ventral Striatum Reward Versus No Reward Condition
Percent change of bold signal in the ventral striatum between conditions p5 and p0 at t2 - % change of bold signal in ventral striatum between conditions p5 and p0 at t1. t1= baseline scan; t2= scan performed 2 hours after LPS/saline. P5= $5 reward; p0=no reward. Data only collected at 2 timepoints.
Measured: Baseline line; 2-3 hours
Change in Temperature
Body temperature measured in degrees Fahrenheit.
Measured: 4-hours
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Insula (Interoceptive vs Exteroceptive Condition)
Percent change of bold signal in the insula between exteroceptive and interoceptive conditions at t2 - % change of bold signal in insula between exteroceptive and interoceptive conditions at t1. t1= baseline scan; t2= scan performed 2 hours after LPS/saline. Data only collected at 2 timepoints.
Measured: Baseline line 2-3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2017
- Study start7 Sep 2017
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Savitz, Laureate Institute for Brain Research, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142919
- Sponsor's protocol ID
- 2016-002-00
- Status last verified
- Jun 2025
- First submitted
- 28 Apr 2017
- Last updated
- 2 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response to Inflammatory Challenge in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT03142919
- Acronym / sponsor ID
- 2016-002-00
- Conditions
- Major Depressive Disorder
- Keywords
- Mood Disorder, MDD, Endotoxin, MRI, CRP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 8 May 2017 (actual)
- Results
- Posted 2 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| High CRP LPS Intervention | Experimental | Biological: LipopolysaccharideHigh CRP Individuals with Major Depressive Disorder receiving LPS intervention |
| Low CRP LPS Intervention | Active comparator | Biological: LipopolysaccharideLow CRP Individuals with Major Depressive Disorder receiving LPS intervention |
| High CRP LPS Placebo | Placebo comparator | Biological: PlaceboHigh CRP Individuals with Major Depressive Disorder receiving placebo |
| Low CRP LPS Placebo | Placebo comparator | Biological: PlaceboLow CRP Individuals with Major Depressive Disorder receiving placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (40 listed)
- 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.
- Pregnancy
- Previous history of fainting during blood draws.
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LipopolysaccharideAlso: Endotoxin, CCRELipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative | Biological | High CRP LPS Intervention, Low CRP LPS Intervention |
| PlaceboAlso: Saline solutionSaline solution | Biological | High CRP LPS Placebo, Low CRP LPS Placebo |
Primary outcome
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: 2-hours
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.
7 secondary outcomes
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 24 hours
Change in Interleukin 6 (IL-6) Protein Levels
Time frame: 2-hours
Change in Interleukin 10 (IL-10) Protein Levels
Time frame: 2-hours
Change in Tumor Necrosis Factor (TNF) Protein Levels
Time frame: 2-hours
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Ventral Striatum Reward Versus No Reward Condition
Time frame: Baseline line; 2-3 hours
Change in Temperature
Time frame: 4-hours
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Insula (Interoceptive vs Exteroceptive Condition)
Time frame: Baseline line 2-3 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Major Depressive Disorder
RecruitingPhase 2
Double-blind, Placebo-controlled Study in Adults With Major Depressive Disorder
Major Depressive Disorder (MDD)
RecruitingPhase 2
A Study to Evaluate the Safety and Efficacy of ALKS 7290 as an Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder
Major Depressive Disorder (MDD)
Recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
Digital Intervention for Physical Activity
Depression - Major Depressive Disorder, Anxiety
Recruiting
Ketogenic Diet and Neuromodulation in Treatment Resistant Depression
Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lipopolysaccharide in people with Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Snaith-Hamilton Pleasure Scale (SHAPS) (time frame: 2-hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.