Depression DisordersNCT07211087
Improving the Treatment of Depression Among Youth With HIV
A study testing COMBEX and COMB in people with Depression Disorders and HIV (Human Immunodeficiency Virus), run by Rhode Island Hospital.
Trial summary
Depression is a common psychiatric condition among Youth with HIV (YWH), with prevalence as high as 25% in the United States. The treatment of depression is essential for improving both psychiatric and medical outcomes for YWH (e.g., adherence to antiretroviral treatment). Read more about this study
- Who is it for?
- Ages 15 to 24 years
- Conditions the study is for
- Depression Disorders, HIV (Human Immunodeficiency Virus)
- What is being tested?
- COMBEX and COMB
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2026to 1 Jul 2029
- Phase
- Interventional
- 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 15 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- aged 15- 24 years
- engaged in care at a participating HIV care site
- have documented HIV-1 confirmed by medical records
- a diagnosis as determined by a site clinician of nonpsychotic depression requiring treatment [either Major Depressive Disorder (MDD), Depression not otherwise specified, or Dysthymia as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
- significant symptomatology at Entry (as defined by the PHQ-9)
- aware of their HIV status as determined by site staff
- English-speaking
- able and willing to provide written informed assent/consent and written parental or guardian permission
Who cannot join
- by site review, have a history of any psychotic disorders and/or Bipolar I or II Disorder
- have of a severe alcohol or substance dependence according to DSM-V or had moderate symptoms and are experiencing withdrawal or dependence symptoms within the month prior to enrollment
- have depression and/or suicidal ideation requiring more intensive services
- intend to relocate from the study site; 5) are in therapy with a non-study therapist (unless willing to switch to a study-trained therapist)
- if they are in imminent danger to themselves or others. If wards of the state meet all eligibility requirements, they will be eligible if the state allows them to participate in research. Otherwise, they will be excluded.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Depression is a common psychiatric condition among Youth with HIV (YWH), with prevalence as high as 25% in the United States. The treatment of depression is essential for improving both psychiatric and medical outcomes for YWH (e.g., adherence to antiretroviral treatment). Practice guidelines for the treatment of depression and substantial research (including for those with and without HIV), indicate that measured-care treatment (care decisions guided by systematic symptom measurement) and using a combination of a medication management algorithm (MMA) and cognitive behavioral therapy (CBT) that is tailored to the population is efficacious. Unfortunately, these methods are seldom fully implemented in practice, leading to markedly reduced intervention effectiveness.
This proposed project will compare an enhanced version of combination treatment (COMBEX) to our previously tested combination treatment (COMB) in a Hybrid Type 2 Cluster Randomized Trial. COMBEX will be enhanced by five ERIC implementation strategies as suggested in our post-trial interviews from our efficacy trial and it will also continue to use the ERIC strategies used in COMB. It is hypothesized that these additional ERIC strategies will improve sustainability and depression outcomes at 48 and 72 weeks.
Read the detailed description
Depression is a common psychiatric condition among Youth with HIV (YWH), with prevalence as high as 25% in the United States. The treatment of depression is essential for improving both psychiatric and medical outcomes for YWH (e.g., adherence to antiretroviral treatment). Practice guidelines for the treatment of depression and substantial research (including for those with and without HIV), indicate that measured-care treatment (care decisions guided by systematic symptom measurement) and using a combination of a medication management algorithm (MMA) and cognitive behavioral therapy (CBT) that is tailored to the population is efficacious. Unfortunately, these methods are seldom fully implemented in practice, leading to markedly reduced intervention effectiveness.
This proposed project will compare an enhanced version of combination treatment (COMBEX) to our previously tested combination treatment (COMB) in a Hybrid Type 2 Cluster Randomized Trial. COMBEX will be enhanced by five ERIC implementation strategies as suggested in our post-trial interviews from our efficacy trial and it will also continue to use the ERIC strategies used in COMB. It is hypothesized that these additional ERIC strategies will improve sustainability and depression outcomes at 48 and 72 weeks.
The specific co-primary aims of this proposed study are to:
- Test the effectiveness COMBEX (with its additional ERIC strategies) compared to COMB on the implementation outcomes of adoption, fidelity, and sustainability.
- Evaluate, using a cluster randomized design, the impact of COMBEX compared to COMB in improving real-world effectiveness of reducing indices of depression (e.g., symptoms, treatment response, remission) and decreasing the viral load (VL) among 130 YWH in eight HIV care clinics over 72 weeks.
- Use an explanatory, sequential, mixed-method approach to evaluate the context of implementation, for both COMB and COMBEX, guided by the sustainability framework with data from staff/clinicians (n=64).
- Being tested
- COMBEX, COMB
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COMBEXBehavioural
The intervention (COMBEX) is a combined approach to routine psychotherapy (including CBT and medication management) with additional ERIC strategies incorporated.
COMBBehavioural
COMB is a combined approach to routine psychotherapy (including CBT and medication management).
| Study group | Role | What they receive |
|---|---|---|
| COMBEX | Experimental | COMB + additional ERIC strategies Receives: Behavioral: COMBEX |
| COMB | Active comparator | Combined approach to routine psychotherapy (including CBT and medication management) Receives: Behavioral: COMB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient Health Questionnaire-9 (PHQ-9)
Self-reported depression symptoms score
Measured: Assessed at baseline and Weeks 12, 24, 36, 48, 60, and 72
Secondary outcomes (1)
HIV viral load
Quantitative VL levels (copies/mL) will be abstracted from the medical records
Measured: Measured at baseline and Weeks 12, 24, 36, 48, 60, and 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2025
- Study start1 Apr 2026 (estimated)
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2029 (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 Depression DisordersStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Hybrid Type 2 Cluster Randomized Trial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Larry K Brown, MD, Principal investigator, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07211087
- Sponsor's protocol ID
- R01MH137280
- Other IDs
- R01MH137280
- Status last verified
- Feb 2026
- First submitted
- 29 Sep 2025
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Hugunin J, Emslie G, Kennard B, Elwy AR, Barker D, Arnold T, Dougherty QH, Whiteley L, Brown LK. A hybrid type 2 cluster randomized trial of an enhanced combined cognitive behavioral therapy and medication management algorithm for treatment of depression among youth living with HIV: study protocol. Implement Sci. 2026 Jul 17. doi: 10.1186/s13012-026-01528-w. Online ahead of print.
PubMed 42469890
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving the Treatment of Depression Among Youth With HIV
- ClinicalTrials.gov ID
- NCT07211087
- Acronym / sponsor ID
- R01MH137280
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 7 Oct 2025 (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.
Depression is a common psychiatric condition among Youth with HIV (YWH), with prevalence as high as 25% in the United States. The treatment of depression is essential for improving both psychiatric and medical outcomes for YWH (e.g., adherence to antiretroviral treatment). Practice guidelines for the treatment of depression and substantial research (including for those with and without HIV), indicate that measured-care treatment (care decisions guided by systematic symptom measurement) and using a combination of a medication management algorithm (MMA) and cognitive behavioral therapy (CBT) that is tailored to the population is efficacious. Unfortunately, these methods are seldom fully implemented in practice, leading to markedly reduced intervention effectiveness.
This proposed project will compare an enhanced version of combination treatment (COMBEX) to our previously tested combination treatment (COMB) in a Hybrid Type 2 Cluster Randomized Trial. COMBEX will be enhanced by five ERIC implementation strategies as suggested in our post-trial interviews from our efficacy trial and it will also continue to use the ERIC strategies used in COMB. It is hypothesized that these additional ERIC strategies will improve sustainability and depression outcomes at 48 and 72 weeks.
Detailed description
Depression is a common psychiatric condition among Youth with HIV (YWH), with prevalence as high as 25% in the United States. The treatment of depression is essential for improving both psychiatric and medical outcomes for YWH (e.g., adherence to antiretroviral treatment). Practice guidelines for the treatment of depression and substantial research (including for those with and without HIV), indicate that measured-care treatment (care decisions guided by systematic symptom measurement) and using a combination of a medication management algorithm (MMA) and cognitive behavioral therapy (CBT) that is tailored to the population is efficacious. Unfortunately, these methods are seldom fully implemented in practice, leading to markedly reduced intervention effectiveness.
This proposed project will compare an enhanced version of combination treatment (COMBEX) to our previously tested combination treatment (COMB) in a Hybrid Type 2 Cluster Randomized Trial. COMBEX will be enhanced by five ERIC implementation strategies as suggested in our post-trial interviews from our efficacy trial and it will also continue to use the ERIC strategies used in COMB. It is hypothesized that these additional ERIC strategies will improve sustainability and depression outcomes at 48 and 72 weeks.
The specific co-primary aims of this proposed study are to:
- Test the effectiveness COMBEX (with its additional ERIC strategies) compared to COMB on the implementation outcomes of adoption, fidelity, and sustainability.
- Evaluate, using a cluster randomized design, the impact of COMBEX compared to COMB in improving real-world effectiveness of reducing indices of depression (e.g., symptoms, treatment response, remission) and decreasing the viral load (VL) among 130 YWH in eight HIV care clinics over 72 weeks.
- Use an explanatory, sequential, mixed-method approach to evaluate the context of implementation, for both COMB and COMBEX, guided by the sustainability framework with data from staff/clinicians (n=64).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Hybrid Type 2 Cluster Randomized Trial
| Arm | Type | Receives |
|---|---|---|
| COMBEX | Experimental | Behavioral: COMBEXCOMB + additional ERIC strategies |
| COMB | Active comparator | Behavioral: COMBCombined approach to routine psychotherapy (including CBT and medication management) |
Who may qualify
- Ages
- 15 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- aged 15- 24 years
- engaged in care at a participating HIV care site
- have documented HIV-1 confirmed by medical records
- a diagnosis as determined by a site clinician of nonpsychotic depression requiring treatment [either Major Depressive Disorder (MDD), Depression not otherwise specified, or Dysthymia as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
- significant symptomatology at Entry (as defined by the PHQ-9)
Key exclusion criteria (5 listed)
- by site review, have a history of any psychotic disorders and/or Bipolar I or II Disorder
- have of a severe alcohol or substance dependence according to DSM-V or had moderate symptoms and are experiencing withdrawal or dependence symptoms within the month prior to enrollment
- have depression and/or suicidal ideation requiring more intensive services
- intend to relocate from the study site; 5) are in therapy with a non-study therapist (unless willing to switch to a study-trained therapist)
- if they are in imminent danger to themselves or others. If wards of the state meet all eligibility requirements, they will be eligible if the state allows them to participate in research. Otherwise, they will be excluded.
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 |
|---|---|---|
| COMBEXThe intervention (COMBEX) is a combined approach to routine psychotherapy (including CBT and medication management) with additional ERIC strategies incorporated. | Behavioural | COMBEX |
| COMBCOMB is a combined approach to routine psychotherapy (including CBT and medication management). | Behavioural | COMB |
Primary outcome
Patient Health Questionnaire-9 (PHQ-9)
Time frame: Assessed at baseline and Weeks 12, 24, 36, 48, 60, and 72
Self-reported depression symptoms score
1 secondary outcome
HIV viral load
Time frame: Measured at baseline and Weeks 12, 24, 36, 48, 60, and 72
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 27 Feb 2026.
- Derived from this study: PubMed 42469890Hugunin J, Emslie G, Kennard B, Elwy AR, Barker D, Arnold T, Dougherty QH, Whiteley L, Brown LK. A hybrid type 2 cluster randomized trial of an enhanced combined cognitive behavioral therapy and medication management algorithm for treatment of depression among youth living with HIV: study protocol. Implement Sci. 2026 Jul 17. doi: 10.1186/s13012-026-01528-w. Online ahead of print.
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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.
Larry K Brown, MD principal investigator
Rhode Island Hospital
Questions about this trial
What is this clinical trial studying?
A study testing COMBEX and COMB in people with Depression Disorders and HIV (Human Immunodeficiency Virus), run by Rhode Island Hospital.
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 8 inclusion and 5 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: opening soon, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
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.
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 Larry K Brown, MD ((401)-793-8808, lkbrown@brownhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Health Questionnaire-9 (PHQ-9) (time frame: Assessed at baseline and Weeks 12, 24, 36, 48, 60, and 72). 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 NCT07211087, 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 27 Feb 2026.