Depression, HIV
Conditions
Brief summary
This trial will determine if depression treatment will reduce cardiovascular risk in HIV-infected patients already receiving HIV treatments. Half of the participants will undergo a specific computerized depression treatment with the other half receiving usual care from their HIV providers.
Detailed description
The objectives of this study will be met by performing a 24-week, randomized, controlled, single-blinded, two-arm, parallel group, pilot trial at a single center. A total of 200 subjects may be screened to identify 110 participants to be enrolled and randomized. These participants will be ≥ 18 years old, have been receiving antiretroviral therapy for at least one year with an HIV viral load \< 75 copies/mL at screening, and have major depression using the PHQ-9 questionnaire. These participants will be randomized 1:1 to either depression treatment with the Beating-the-Blues cognitive behavioral therapy program (N=55) or usual care (N=55).
Interventions
BEHAVIORALBeating the Blues
Computerized depression treatment intervention
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection, documented by both: (1) any licensed rapid HIV test or HIV enzyme test kit at any time prior to study entry and (2) by at least one detectable HIV-1 antigen or at least one detectable plasma HIV-1 RNA viral load * Age equal to or greater than 18 years * Receipt of antiretroviral therapy of any kind for at least 360 days prior to screening Note: Interruptions in ART of up to 14 days total during the 360 days prior to screening are allowed * HIV-1 RNA level \< 75 copies/mL at screening NOTE: There are no CD4 cell count eligibility criteria for this trial * For women who are still of reproductive potential, a negative urine pregnancy test * Depression as defined by having a score ≥ 10 on the PHQ-9 questionnaire
Exclusion criteria
* Inability to complete written, informed consent * Incarceration at the time of any study visit * Active suicidality, 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 on the Patient Suicidality Form (with last suicide attempt within the past ten years) * Diagnosed vascular disease (documented history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease) * History of congestive heart failure, even if currently compensated * Diagnosed disease or process, besides HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, other collagen vascular diseases) Note: Hepatitis B or C co-infections are NOT exclusionary * Known or suspected malignancy requiring systemic treatment within 180 days of screening NOTE: Localized treatment for skin cancers is not exclusionary * History of Raynaud's phenomenon * History of cardiac arrhythmias or cardiomyopathy * Uncontrolled hyperthyroidism or hypothyroidism, defined as TSH values outside of the local reference range on most recent clinical assessment * History of carotid bruits * Systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 110 mmHg at screening * Screening estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.732 (using the 2009 CKD-EPI equation) using a serum creatinine level measured at screening * Screening glucose ≥ 140 mg/dL or hemoglobin A1c \> 8.0% * Screening total cholesterol \> 240 mg/dL * Therapy for serious medical illnesses within 14 days prior to screening Note: Therapy for serious medical illnesses that overlaps with a main 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 course of the study * Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids (of any dose), or anabolic steroids at screening 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 * Active drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements * History of schizophrenia or bipolar disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brachial Artery Flow-mediated Dilation From Baseline to Week 12 | Baseline and Week 12 of participation | Changes in flow-mediated dilation of the brachial artery from baseline to week 12. This is calculated by the FMD value at Week 12 minus the FMD value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Circulating IL-6 From Baseline to Week 12 | Baseline and 12 weeks | Interleukin-6 (IL-6) is a measure of systemic inflammation. This is calculated by the IL-6 value at Week 12 minus the IL-6 value at baseline. |
| Change in hsCRP From Baseline to Week 12 | 12 weeks | hsCRP (high sensitivity C-reactive protein) is a measure of systemic inflammation. This is calculated by the hsCRP value at Week 12 minus the hsCRP value at baseline. |
| Change in D-dimer From Baseline to Week 12 | 12 weeks | D-dimer is a measure of systemic coagulation. This is calculated by the D-dimer value at Week 12 minus the D-dimer value at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Behavioral Therapy (CBT) Those assigned to the CBT arm will undergo therapy with the Beating the Blues (BtB) computerized intervention.
Beating the Blues: Computerized depression treatment intervention | 27 |
| Usual Care No specific depression care will be provided through this study for those assigned to this arm. However, the participant's caregiver may choose to provide depression treatment outside of this trial. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
Baseline characteristics
| Characteristic | Usual Care | Total | Cognitive Behavioral Therapy (CBT) |
|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 11.9 | 45.1 years STANDARD_DEVIATION 10.8 | 44.6 years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 36 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 16 Participants | 6 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 22 Participants | 45 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 5 / 27 | 1 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
Change in Brachial Artery Flow-mediated Dilation From Baseline to Week 12
Changes in flow-mediated dilation of the brachial artery from baseline to week 12. This is calculated by the FMD value at Week 12 minus the FMD value at baseline.
Time frame: Baseline and Week 12 of participation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Brachial Artery Flow-mediated Dilation From Baseline to Week 12 | -0.47 absolute percent change | Standard Deviation 2.65 |
| Usual Care | Change in Brachial Artery Flow-mediated Dilation From Baseline to Week 12 | 0.29 absolute percent change | Standard Deviation 2.93 |
p-value: 0.3295% CI: [-2.28, 0.77]t-test, 2 sided
Secondary
Change in D-dimer From Baseline to Week 12
D-dimer is a measure of systemic coagulation. This is calculated by the D-dimer value at Week 12 minus the D-dimer value at baseline.
Time frame: 12 weeks
Population: Participants who had blood samples available for analysis at both baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in D-dimer From Baseline to Week 12 | 3.69 ng/mL | Standard Deviation 466 |
| Usual Care | Change in D-dimer From Baseline to Week 12 | -10.26 ng/mL | Standard Deviation 651 |
Secondary
Change in hsCRP From Baseline to Week 12
hsCRP (high sensitivity C-reactive protein) is a measure of systemic inflammation. This is calculated by the hsCRP value at Week 12 minus the hsCRP value at baseline.
Time frame: 12 weeks
Population: Participants who had blood samples available for analysis at both baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in hsCRP From Baseline to Week 12 | 1.22 mg/L | Standard Deviation 3.89 |
| Usual Care | Change in hsCRP From Baseline to Week 12 | 1.06 mg/L | Standard Deviation 4.71 |
Secondary
Changes in Circulating IL-6 From Baseline to Week 12
Interleukin-6 (IL-6) is a measure of systemic inflammation. This is calculated by the IL-6 value at Week 12 minus the IL-6 value at baseline.
Time frame: Baseline and 12 weeks
Population: Participants who had blood samples available for analysis at both baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Changes in Circulating IL-6 From Baseline to Week 12 | 2.38 pg/mL | Standard Deviation 8.71 |
| Usual Care | Changes in Circulating IL-6 From Baseline to Week 12 | 1.24 pg/mL | Standard Deviation 4.16 |