Major Depressive DisorderPhase 2SOOTHENCT05570812
Neuroactive Steroid to Treat Depressed Mood: A Trial for People With HIV
A Phase 2 study testing Pregnenolone in people with Major Depressive Disorder and Anxiety Depression, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study will determine the effects of pregnenolone on brain function, inflammation and depressive symptoms in people with HIV who have depression. Participants in this study will receive a pill of either pregnenolone or placebo, and can stay on their current antidepression medications. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Major Depressive Disorder, Anxiety Depression, HIV
- What is being tested?
- Pregnenolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2023to 31 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-85 years
- HIV-1 viral load <200 copies/mL on antiretroviral therapy (ART) at screening visit
- Center for Epidemiological Studies - Depression (CES-D) score ≥ 20
Who cannot join
- Contraindication to magnetic resonance imaging (MRI) or poor-quality baseline MRI preventing image analyses as determined by radiologist assessment
- Recent severe infections including opportunistic infections, active bacterial, mycobacterial, fungal, or certain viral infections
- Vulnerable populations (e.g., pregnant/nursing, severe cognitive or intellectual impairment, incarcerated)
- Use of cobicistat or ritonavir
- High risk for suicide (active suicidal ideation (SI) with plan/intent as assessed by using the Columbia Suicide Severity Rating (C-SSRS) or > 2 attempts in lifetime or any in the past 6 months) or expresses homicidal ideation necessitating clinical intervention or representing an imminent concern
- Any severe (life-threatening or unstable) medical condition as determined by clinician assessment
Show all 22Show fewer
- Blood pressure, with the lowest reading taken after three repeat readings during screening visit, ≥ 160 mmHg systolic OR ≥ 95 mmHg diastolic or other life-threatening vital signs as determined by clinician assessment
- Clinically significant abnormalities in physical examination or ECG that would interfere with study participation
- Decompensated cirrhosis, active liver inflammation (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 5 times the upper limit of normal) or unsuppressed viral hepatitis B or C infection
- Severe renal disease (estimated glomerular filtration rate ≤ 30 mL/min/1.73m2)
- Seizure disorder requiring antiepileptic treatment
- History of allergic reaction or side effects with prior pregnenolone use
- Currently using testosterone enanthate, testosterone cypionate, or estrogen containing preparations that significantly increase systemic estrogen levels, including but not limited to oral and transdermal forms of estrogen. All other forms of exogenous sex steroid hormones will be evaluated at the discretion of the PI and/or clinical delegates.
- Currently using systemic immunosuppressive agents, including corticosteroids, chemotherapy, or specific immunomodulating agents, such as monoclonal antibodies and TNF-inhibitors
- Excessive alcohol or other substances use that would interfere with classification of major depression disorder, study procedures and/or follow-up
- Current diagnosis of bipolar disorder
- Diagnosis of a psychotic disorder (current or lifetime)
- Diagnosis of schizophrenia (current or lifetime)
- <70% adherence to study drug prior to randomization
- Inability to swallow pills/capsules
- Not able to complete neuropsychological testing in English
- Concurrent participation in another interventional trial, except for lifestyle and device studies (For vaccination studies, individuals in the observation period are not exclusionary. Other interventions will be evaluated at the discretion of the PI and/or clinical delegates.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Shibani Mukerji, MD, PhD
About this study
Official title: In Vivo Targeting of Neuroactive Steroid and Immune Networks for Depression in People Living With HIV
This study will determine the effects of pregnenolone on brain function, inflammation and depressive symptoms in people with HIV who have depression. Participants in this study will receive a pill of either pregnenolone or placebo, and can stay on their current antidepression medications. Brain imaging and behavioral assessments will be performed during the study.
Read the detailed description
Pregnenolone is a neuroactive steroid that exhibits actions highly relevant to treating depression in people with HIV. The investigators' recent human data suggest that neuroactive steroids are decreased in people with HIV and depression. In addition, multiple groups have reported reductions in neuroactive steroids in people without HIV who have depression. A total of 120 people living with HIV on antiretroviral therapy with depression will be randomized to either pregnenolone or placebo (2 groups/90 participants receiving pregnenolone and 30 participants receiving placebo). Drug dosage will begin at 50 mg daily and incrementally increase to 500 mg daily within the first 4 weeks, with a stable 500 mg/day regimen for the final 4 weeks. Behavioral testing and blood draw will be performed at baseline, 2 weeks, 4 weeks, and 8 weeks, while magnetic resonance spectroscopy (MRS), and task-based functional magnetic resonance imaging (MRI) will be conducted at 2 weeks and 8 weeks.
The investigators hypothesize that pregnenolone will be well-tolerated in people with HIV and depression, and that this intervention may improve brain activity and reduce inflammation.
- Conditions
- Major Depressive Disorder, Anxiety Depression, HIV
- Being tested
- Placebo, Pregnenolone
- Keywords
- HIV, Depression, Neuroactive Steroid, Pregnenolone
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
(4-week ramp, 4-week steady dosing)
PregnenoloneDrug
Also called Neuroactive steroid
(4-week ramp, 4-week steady dosing)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Experimental | Participants will be on the following dosage schedule:
50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks Receives: Drug: Placebo |
| Pregnenolone | Experimental | Participants will be on the following dosage schedule:
50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks Receives: Drug: Pregnenolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gamma-aminobutyric acid (GABA) Concentration
Comparison between Pregnenolone and Placebo Groups of Left Insular Cortex GABA Concentration, Adjusted for Baseline.
Measured: Day 14, Day 56
Secondary outcomes (5)
Center for Epidemiological Studies-Depression (CES-D; scores range from 0 (no symptoms) to 60 (maximum severity of depressive symptoms))
Comparison of Percentage of Pregnenolone and Placebo Groups Showing Clinical Improvement of Depression at Study End. The revised CES-D is administered, and the total score is calculated by adding the responses to the 20 questions.
Measured: Day 0, Day 14, Day 56
CD14+CD16+ Monocytes
Comparison of the Percentage of CD14+CD16+ Monocytes Over Time Adjusted for Baseline Between Pregnenolone and Placebo Groups
Measured: Day 0, Day 14, Day 28, Day 56
GABA Concentration in Responders
Comparison of Baseline Left Insular Cortex GABA and Pregnenolone Between Participants in Pregnenolone Group with Clinical Improvement Compared to Clinical Non-Improvers in Pregnenolone Group
Measured: Day 0, Day 14, Day 56
Adverse Events
Comparison of the Incidence and Severity of Adverse Events Between Pregnenolone and Placebo Groups
Measured: Day 14, Day 56
Dose Modifications
Comparison of Dose Modifications Required Between Pregnenolone and Placebo Groups
Measured: Day 14, Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2022
- Study start3 Mar 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to receive oral pregnenolone or placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Institute for Medical Research, Inc.
- Responsible party
- Principal investigator, Shibani Mukerji, Massachusetts General Hospital
- Investigators
- Shibani S. Mukerji, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05570812
- Sponsor's protocol ID
- 2022P001941
- Other IDs
- 1R01MH131194-01
- Acronym
- SOOTHE
- Status last verified
- Sep 2025
- First submitted
- 4 Oct 2022
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mukerji SS, Misra V, Lorenz DR, Chettimada S, Keller K, Letendre S, Ellis RJ, Morgello S, Parker RA, Gabuzda D. Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy. J Infect Dis. 2021 May 20;223(9):1601-1611. doi: 10.1093/infdis/jiaa104.
PubMed 32157292
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo Targeting of Neuroactive Steroid and Immune Networks for Depression in People Living With HIV
- ClinicalTrials.gov ID
- NCT05570812
- Acronym / sponsor ID
- SOOTHE / 2022P001941
- Conditions
- Major Depressive Disorder, Anxiety Depression, HIV
- Keywords
- HIV, Depression, Neuroactive Steroid, Pregnenolone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Institute for Medical Research, Inc.
- Study start
- 3 Mar 2023 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 7 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the effects of pregnenolone on brain function, inflammation and depressive symptoms in people with HIV who have depression. Participants in this study will receive a pill of either pregnenolone or placebo, and can stay on their current antidepression medications. Brain imaging and behavioral assessments will be performed during the study.
Detailed description
Pregnenolone is a neuroactive steroid that exhibits actions highly relevant to treating depression in people with HIV. The investigators' recent human data suggest that neuroactive steroids are decreased in people with HIV and depression. In addition, multiple groups have reported reductions in neuroactive steroids in people without HIV who have depression. A total of 120 people living with HIV on antiretroviral therapy with depression will be randomized to either pregnenolone or placebo (2 groups/90 participants receiving pregnenolone and 30 participants receiving placebo). Drug dosage will begin at 50 mg daily and incrementally increase to 500 mg daily within the first 4 weeks, with a stable 500 mg/day regimen for the final 4 weeks. Behavioral testing and blood draw will be performed at baseline, 2 weeks, 4 weeks, and 8 weeks, while magnetic resonance spectroscopy (MRS), and task-based functional magnetic resonance imaging (MRI) will be conducted at 2 weeks and 8 weeks.
The investigators hypothesize that pregnenolone will be well-tolerated in people with HIV and depression, and that this intervention may improve brain activity and reduce inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to receive oral pregnenolone or placebo.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Experimental | Drug: PlaceboParticipants will be on the following dosage schedule: 50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks |
| Pregnenolone | Experimental | Drug: PregnenoloneParticipants will be on the following dosage schedule: 50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18-85 years
- HIV-1 viral load <200 copies/mL on antiretroviral therapy (ART) at screening visit
- Center for Epidemiological Studies - Depression (CES-D) score ≥ 20
Key exclusion criteria (22 listed)
- Contraindication to magnetic resonance imaging (MRI) or poor-quality baseline MRI preventing image analyses as determined by radiologist assessment
- Recent severe infections including opportunistic infections, active bacterial, mycobacterial, fungal, or certain viral infections
- Vulnerable populations (e.g., pregnant/nursing, severe cognitive or intellectual impairment, incarcerated)
- Use of cobicistat or ritonavir
- High risk for suicide (active suicidal ideation (SI) with plan/intent as assessed by using the Columbia Suicide Severity Rating (C-SSRS) or > 2 attempts in lifetime or any in the past 6 months) or expresses homicidal ideation necessitating clinical intervention or representing an imminent concern
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 |
|---|---|---|
| Placebo(4-week ramp, 4-week steady dosing) | Drug | Placebo |
| PregnenoloneAlso: Neuroactive steroid(4-week ramp, 4-week steady dosing) | Drug | Pregnenolone |
Primary outcome
Gamma-aminobutyric acid (GABA) Concentration
Time frame: Day 14, Day 56
Comparison between Pregnenolone and Placebo Groups of Left Insular Cortex GABA Concentration, Adjusted for Baseline.
5 secondary outcomes
Center for Epidemiological Studies-Depression (CES-D; scores range from 0 (no symptoms) to 60 (maximum severity of depressive symptoms))
Time frame: Day 0, Day 14, Day 56
CD14+CD16+ Monocytes
Time frame: Day 0, Day 14, Day 28, Day 56
GABA Concentration in Responders
Time frame: Day 0, Day 14, Day 56
Adverse Events
Time frame: Day 14, Day 56
Dose Modifications
Time frame: Day 14, Day 56
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Background: PubMed 32157292Mukerji SS, Misra V, Lorenz DR, Chettimada S, Keller K, Letendre S, Ellis RJ, Morgello S, Parker RA, Gabuzda D. Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy. J Infect Dis. 2021 May 20;223(9):1601-1611. doi: 10.1093/infdis/jiaa104.
- Individual participant dataSharing planned: No
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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.
Shibani S. Mukerji, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pregnenolone in people with Major Depressive Disorder and Anxiety Depression, run by Massachusetts General Hospital 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 3 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 12 Sep 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hemi Park, MPH (857-282-3788, MGHSOOTHE@PARTNERS.ORG), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gamma-aminobutyric acid (GABA) Concentration (time frame: Day 14, Day 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05570812, which also lists 1 linked publication.
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 12 Sep 2025.