HIVNCT07226128
The Effects of Cognitive Behavioral Therapy on Insulin Resistance in People With HIV
A study testing Internet cognitive behavioral therapy (iCBT-D) in people with HIV and Depression in Adults, run by Indiana University at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if depression treatment improves insulin resistance, or how the body uses insulin to lower blood sugar, in people with HIV on HIV treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Depression in Adults, Insulin Resistance
- What is being tested?
- Internet cognitive behavioral therapy (iCBT-D)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2026to 31 Aug 2029
- Phase
- Interventional
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented as listed clinically in the participant's electronic medical record by any of the following tests: (1) any licensed rapid HIV test, (2) HIV enzyme test kit at any time prior to study entry, (3) at least one detectable HIV-1 antigen, or (4) at least one detectable plasma HIV-1 RNA viral load.
- Age ≥ 18 years.
- Ongoing receipt of stable antiretroviral therapy of any kind for at least 180 days prior to Screening
- Meets the depression definition for this trial:
- (1) repeat PHQ-9 ≥10100 result at the Screening Visit (suggesting moderate to severe depressive symptoms), AND
- (2) PHQ-9 depressive disorder diagnosis (2 or more of the 9 depressive symptoms, including depressed mood or anhedonia, present in the past 2 weeks), AND
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- (3) functional impairment (using the tenth PHQ-9 item assessing social/occupational impairment), AND
- (4) no evidence that the direct physiological effects of a substance, medication, or medical condition clearly account for the depressive symptoms, AND
- (5) no bipolar or psychotic disorders
- NOTE: The use of antidepressant medications is not exclusionary.
- HbA1c < 6.5% at Screening
- HIV-1 RNA level < 75 copies/mL at Screening
- NOTE: There are no CD4 cell count eligibility criteria for this trial.
Who cannot join
- Inability to complete written, informed consent
- Inability to read and understand English as seen on a computer screen
- Diagnosed diabetes mellitus or any previously recorded HbA1c ≥6.5%
- History of bipolar disorder or a psychotic disorder, including schizophrenia
- NOTE: Depressive disorders are not exclusionary.
- Incarceration at the time of any study visit
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- Active suicidality at Entry, as determined by the patient's HIV provider or social worker following a positive response (1, 2, or 3) to PHQ-9 Item #9 and a positive response (yes) to one or more of the three questions (for Question #3, the previous attempt must be within the past 10 years) on the Patient Suicidality Form (see Appendix).
- Diagnosed disease or process, besides HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosus, inflammatory bowel diseases, or other collagen vascular diseases).
- NOTE: Hepatitis B or C co-infections are NOT exclusionary, but treatment for hepatitis C cannot be provided during study participation
- End stage renal disease requiring renal replacement therapy (dialysis, transplantation).
- Known or suspected malignancy requiring systemic treatment within 180 days of the Entry Visit.
- NOTE: Localized treatment for skin cancers is not exclusionary.
- Therapy for serious medical illnesses within 14 days prior to the Entry Visit
- NOTE: Therapy for serious medical illnesses that overlaps with a study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.
- Pregnancy or breastfeeding during the study.
- Receipt of investigational agents, cytotoxic chemotherapy, systemic immunosuppressive therapies, systemic glucocorticoids (of any dose), or anabolic steroids at the Entry Visit
- NOTE: Physiologic testosterone replacement therapy or topical steroids is not exclusionary. Inhaled/nasal steroids are not exclusionary as long as the participant is not also receiving HIV protease inhibitors
- NOTE: Use of NSAIDS and aspirin are allowed
- Active drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
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
Indiana University Health
Indianapolis, Indiana, 46202
Danielle Grounds, 317-278-0255, diground@iu.edu
About this study
Official title: A Randomized, Controlled Trial Assessing the Effects of Cognitive Behavioral Therapy to Prevent Worsening Insulin Resistance in Depressed, Virologically-Suppressed, Antiretroviral-Treated Adults With HIV
The goal of this clinical trial is to learn if depression treatment improves insulin resistance, or how the body uses insulin to lower blood sugar, in people with HIV on HIV treatment. Researchers will compare an internet-based (online) depression treatment program called cognitive behavioral therapy with depression education. In the online group, participants will undergo 9 weekly treatment sessions. The education group will receive learning materials about depression and will be monitored every month. All participants will have 4 study visits over 12 months.
- Being tested
- Internet cognitive behavioral therapy (iCBT-D), Active Control (AC)
- Keywords
- hiv, depression, insulin resistance, diabetes, cognitive behavioral therapy
- Medical subject headings
- Insulin Resistance, Acquired Immunodeficiency Syndrome, Depression, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Internet cognitive behavioral therapy (iCBT-D)Behavioural
Intervention participants will receive the empirically supported, HIPAA-compliant, therapist-assisted iCBT-D called Good Days Ahead (GDA; MindStreet, Inc.). GDA uses an interactive, multimedia format (including video, exercises, calls to action, newsfeeds, and customized feedback) to deliver nine 45-minute sessions, the structure and content of which mirror traditional face-to-face CBT. Topics include identifying and modifying automatic thoughts, using behavioral activation and other behavioral methods, identifying and modifying schemas, using effective coping strategies, and employing other core CBT methods.
Active Control (AC)Behavioural
Our AC comparator will include depression education and depressive symptom monitoring along with usual depression care as provided by the participants HIV clinicians. Trial staff will fist have a 30-minute call with AC participants to review depression materials, including their HIV provider's role in its management and treatment options and also provide a list of local mental health services. There are no care restrictions by the primary HIV clinicians. Trial staff will call AC participants every 4 weeks to assess depressive symptoms (PHQ-9) and will notify clinic staff to encourage additional care when indicated.
| Study group | Role | What they receive |
|---|---|---|
| Internet Cognitive Behavioral Therapy (iCBT-D) | Experimental | Intervention participants will receive the empirically supported, HIPAA-compliant, therapist-assisted iCBT-D called Good Days Ahead (GDA; MindStreet, Inc.).
GDA uses an interactive, multimedia format (including video, exercises, calls to action, newsfeeds, and customized feedback) to deliver nine 45-minute sessions, the structure and content of which mirror traditional face-to-face CBT. Topics include identifying and modifying automatic thoughts, using behavioral activation and other behavioral methods, identifying and modifying schemas, using effective coping strategies, and employing other core CBT methods. Receives: Behavioral: Internet cognitive behavioral therapy (iCBT-D) |
| Active Control (AC) | Active comparator | Our AC comparator will include depression education and depressive symptom monitoring along with usual depression care as provided by the participants HIV clinicians. Trial staff will fist have a 30-minute call with AC participants to review depression materials, including their HIV provider's role in its management and treatment options and also provide a list of local mental health services. There are no care restrictions by the primary HIV clinicians. Trial staff will call AC participants every 4 weeks to assess depressive symptoms (PHQ-9) and will notify clinic staff to encourage additional care when indicated. Receives: Behavioral: Active Control (AC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in HOMA-IR at 24 weeks
Homeostasis Model Assessment-Insulin, where higher values indicate greater insulin resistance
Measured: 24 weeks
Secondary outcomes (9)
Change from baseline in circulating sCD14 at 24 weeks
sCD14 is a blood measure of inflammation, where higher levels indicate greater amounts specifically of monocyte activation
Measured: 24 weeks
Change from baseline in circulating REG3a at 24 weeks
REG3a is a blood measure of gut integrity, where higher levels indicate greater amounts of gut wall breakdown
Measured: 24 weeks
Change from baseline in circulating 16S rDNA at 24 weeks
16S rDNA is a measure of small amounts of bacteria in the blood that typically cannot be grown on blood cultures, where higher amounts indicate more bacteria in the bloodstream
Measured: 24 weeks
Changes from baseline in circulating b-D-glucan at 24 weeks
b-D-glucan is a measure of small amounts of fungus in the blood that typically cannot be grown in fungal cultures, where higher amounts indicate more fungus in the bloodstream
Measured: 24 weeks
Change from baseline in HOMA-IR at 48 weeks
Homeostasis Model Assessment-Insulin, where higher values indicate greater insulin resistance
Measured: 48 weeks
Change from baseline in HbA1c at 24 weeks and 48 weeks
HbA1c (hemoglobin A1c) is a measure of average blood sugar control over 3 months
Measured: 24, 48 weeks
Change from baseline in glycated albumin at 24 weeks and 48 weeks
Glycated albumin is a measure of average blood glucose control over 1 month
Measured: 24, 48 weeks
Change from baseline in circulating sCD163 at 24 weeks
sCD163 is a measure of inflammation, where higher levels indicate greater macrophage activation
Measured: 24 weeks
Change from baseline in PC(P-16:0/18:2) levels at 24 weeks
PC(P-16:0/18:2) is a cell metabolite, where higher levels indicate greater insulin resistance
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start10 Apr 2026
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies 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
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samir K. Gupta, MD, Indiana University
- Investigators
- Samir K Gupta, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226128
- Sponsor's protocol ID
- 28855
- Other IDs
- R01DK141366
- Status last verified
- Aug 2026
- First submitted
- 5 Nov 2025
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD
Publications
Bourgi K, Kundu S, Stewart JC, So-Armah K, Freiberg M, Gupta SK. Associations of HIV and Depression with Incident Diabetes Mellitus: Veterans Aging Cohort Study. Clin Infect Dis. 2022 Feb 3;78(2):378-85. doi: 10.1093/cid/ciac085. Online ahead of print.
PubMed 35134838Gupta SK, Slaven JE, Liu Z, Polanka BM, Freiberg MS, Stewart JC. Effects of Internet Cognitive-Behavioral Therapy on Depressive Symptoms and Surrogates of Cardiovascular Risk in Human Immunodeficiency Virus: A Pilot, Randomized, Controlled Trial. Open Forum Infect Dis. 2020 Jul 5;7(7):ofaa280. doi: 10.1093/ofid/ofaa280. eCollection 2020 Jul.
PubMed 32760749