HIV-related Insomnia and Inflammation

Treating Insomnia to Reduce Inflammation in HIV

This randomized trial will determine the effects of internet cognitive behavioral therapy on measures of systemic inflammation in HIV-positive people receiving antiretroviral therapy.

Study Overview

• Status: Completed
• Conditions: Insomnia; Hiv
• Intervention / Treatment: Device: SHUTi; Behavioral: Sleep Education/Hygiene

Detailed Description

The primary objective of this pilot trial is to evaluate the effects of cognitive behavioral therapy for insomnia (CBT-I) on changes in circulating levels of hsCRP at 24 weeks in virologically-suppressed, HIV-positive adults with insomnia, defined as having an Insomnia Severity Index (ISI) score ≥ 11. Secondary objectives include comparing changes in hsCRP at 12 weeks, changes in other circulating inflammation biomarkers (IL-6, sCD14, sCD163, CD14+CD16+ monocytes) at both 12 and 24 weeks, and ISI scores and other self-reported patient outcomes at both 12 and 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Infectious Diseases Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 equal to or greater than 18 years.
• Ongoing receipt of stable antiretroviral therapy of any kind for at least 180 days prior to the date of the HIV-1 RNA value determining eligibility.
• HIV-1 RNA level < 75 copies/mL at Screening.

NOTE: There are no CD4 cell count eligibility criteria for this trial.

-ISI score ≥ 11 at Screening.

NOTE: Use of sleeping aids/medications is permitted as long as the ISI score criterion is met.

Exclusion Criteria:

• Inability to complete written, informed consent.
• Incarceration at the time of any study visit.
• 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 course of 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.

• Active drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• History of bipolar disorder or a psychotic disorder, including schizophrenia.

NOTE: Depressive disorders are not exclusionary.

• Current sleep disorder diagnosis other than insomnia disorder (e.g., sleep apnea).
• Have a schedule requiring a bedtime earlier than 8:00pm or later than 2:00am or arising time earlier than 4:00am or later than 10:00am (thus preventing adoption of SHUTi interventions).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBT-I; This arm will receive internet CBT-I using SHUTi, a validated and proven therapy provided via internet in the general population.	Device: SHUTi; SHUTi is the empirically supported, internet CBT-I that is fully accessible via tablets and smartphones. It uses a self-guided, fully automated, interactive, multimedia format to deliver six 45-minute sessions, the structure and content of which mirror traditional face-to-face CBT-I. Session content includes sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and relapse prevention. SHUTi is enhanced through a variety of interactive features, including personalized goal setting, graphical feedback based on inputted symptoms, animations and illustrations to enhance comprehension, quizzes to test user knowledge, patient vignettes, and video-based expert explanation. Across sessions, patients also receive tailored sleep recommendations and feedback based on the sleep diary data they enter into the program.
Active Comparator: Sleep Education/Hygiene; This arm will receive best practices education on sleep hygiene.	Behavioral: Sleep Education/Hygiene; A research assistant (RA) will deliver the active control procedures. During the first 4 weeks, the RA will have two calls with each control participant - one 45-minute call on insomnia education (including their HIV provider's role in its management) and one 45-minute call on sleep hygiene practices. To end the first call, the RA will email or mail a list of local behavioral health services to patients and will encourage them to follow-up with their HIV provider. We will then notify the HIV provider, which will encourage them to address their patient's insomnia and provide the same list of local services.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hsCRP Levels at 24 Weeks	Circulating high sensitivity C-reactive protein levels will be measured	Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insomnia Severity Index (ISI) at 24 Weeks	The Insomnia Severity Index (ISI) total score will be measured. The total scale has a minimum score of 0 and a maximum score of 28, with higher scores indicating a worse outcome.	Baseline and 24 weeks
Change in IL-6 Levels at 24 Weeks	Circulating interleukin-6 levels will be measured. Interleukin-6 is a measure of systemic inflammation.	Baseline and 24 weeks
Change is sCD14 Levels at 24 Weeks	Circulating soluble CD14 levels will be measured. Soluble CD14 is a measure of monocyte activation.	Baseline and 24 weeks
Change in sCD163 Levels at 24 Weeks	Circulating soluble CD163 levels will be measured. Soluble CD163 is a measure of monocyte/macrophage activation.	Baseline and 24 weeks
Change in CD14+CD16+ Monocytes at 24 Weeks	Circulating intermediate monocytes as defined by flow cytometric evaluation for CD14+CD16+ monocytes will be measured. CD14+CD16+ monocytes are measured by flow cytometry and indicate the pro-inflammatory subpopulation of monocytes.	Baseline and 24 weeks
Change in hsCRP Levels at 12 Weeks	Circulating high sensitivity C-reactive protein (hsCRP) levels will be measured. hsCRP is a measure of systemic inflammation.	Baseline and 12 weeks
Change in Pittsburgh Sleep Quality Index (PSQI) at 24 Weeks	Changes in the Pittsburgh Sleep Quality Index (PSQI) questionnaire global scores will be measured. The global PSQI score has a range from 0 to 21, with higher numbers indicating worse sleep quality.	Baseline and 24 weeks
Change in Dysfunctional Beliefs and Attitudes About Sleep (DBAS-16) at 24 Weeks	The Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) questionnaire total scores will be measured. The DBAS-16 total score ranges from 0 to 10, with higher scores indicating more dysfunctional beliefs and attitudes about sleep.	Baseline and 24 weeks
Change in Patient Health Questionnaire-9 (PHQ-9) at 24 Weeks	Patient Health Questionnaire (PHQ-9) scores will be measured. The PHQ-9 ranges from 0 to 27, with higher scores indicating worse depression symptom severity.	Baseline and 24 weeks
Change in Hopkins Symptom Checklist (SCL-20) at 24 Weeks	The Hopkins Symptom Checklist (SCL-20) questionnaire score will be measured. The SCL-20 questionnaire scores range from 0 to 4, where higher scores indicate more severe depressive symptoms.	Baseline and 24 weeks
Change in Generalized Anxiety Disorder-7 (GAD-7) at 24 Weeks	The Generalized Anxiety Disorder-7 (GAD-7) questionnaire total score will be measured. The GAD-7 total score ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms.	Baseline and 24 weeks
Change in PROMIS FACIT-F Fatigue Short Form at 24 Weeks	The Patient-Reported Outcomes Measurement Information System (PROMIS) Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) subscale questionnaire score ranges from 0 to 52, with higher scores indicating greater fatigue.	Baseline and 24 weeks
Change in Alcohol Use Disorders Identification Test (AUDIT) at 24 Weeks	Alcohol Use Disorders Identification Test (AUDIT) questionnaire total scores will be measured. The AUDIT total score ranges from 0 to 40, with higher scores indicating greater likelihood of alcohol dependence.	Baseline and 24 weeks
Change in Short Form-36 (SF-36) Health Survey and 24 Weeks	Short Form-36 (SF-36) general health total questionnaire scores will be measured. The SF-36 general health total score ranges from 0 to 100, with higher scores indicating better general health.	Baseline and 24 weeks
Use of Sleep Medications at Week 12	The number of sleep medications used by each participant at Week 12	Week 12
Use of Sleep Medications at Week 24	The number of sleep medications used by each participant at Week 24	Week 24
Insomnia Treatment Satisfaction at Week 12	An assessment of the participant's satisfaction with their assigned insomnia treatment at Week 12, ranging from 1-5, with lower scores indicating greater overall treatment satisfaction.	Week 12
Insomnia Treatment Satisfaction at Week 24	An assessment of the participant's satisfaction with their assigned insomnia treatment at Week 24, ranging from 1-5, with lower scores indicating greater overall treatment satisfaction.	Week 24
Change in Pittsburgh Sleep Quality Index (PSQI) at 12 Weeks	Changes in the Pittsburgh Sleep Quality Index (PSQI) questionnaire global scores will be measured. The global PSQI score has a range from 0 to 21, with higher numbers indicating worse sleep quality.	Baseline and 12 weeks
Change in Dysfunctional Beliefs and Attitudes About Sleep (DBAS-16) at 12 Weeks	The Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) questionnaire total scores will be measured. The DBAS-16 total score ranges from 0 to 10, with higher scores indicating more dysfunctional beliefs and attitudes about sleep.	Baseline and 12 weeks
Change in Patient Health Questionnaire-9 (PHQ-9) at 12 Weeks	Patient Health Questionnaire (PHQ-9) scores will be measured. The PHQ-9 ranges from 0 to 27, with higher scores indicating worse depression symptom severity.	Baseline and 12 weeks
Change in Hopkins Symptom Checklist (SCL-20) at 12 Weeks	The Hopkins Symptom Checklist (SCL-20) questionnaire score will be measured. The SCL-20 questionnaire scores range from 0 to 4, where higher scores indicate more severe depressive symptoms.	Baseline and 12 weeks
Change in Generalized Anxiety Disorder-7 (GAD-7) at 12 Weeks	The Generalized Anxiety Disorder-7 (GAD-7) questionnaire total score will be measured. The GAD-7 total score ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms.	Baseline and 12 weeks
Change in PROMIS FACIT-F Fatigue Short Form at 12 Weeks	The Patient-Reported Outcomes Measurement Information System (PROMIS) Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) subscale questionnaire score ranges from 0 to 52, with higher scores indicating greater fatigue.	Baseline and 12 weeks
Change in Alcohol Use Disorders Identification Test (AUDIT) at 12 Weeks	Alcohol Use Disorders Identification Test (AUDIT) questionnaire total scores will be measured. The AUDIT total score ranges from 0 to 40, with higher scores indicating greater likelihood of alcohol dependence.	Baseline and 12 weeks
Change in Short Form-36 (SF-36) Health Survey and 12 Weeks	Short Form-36 (SF-36) general health total questionnaire scores will be measured. The SF-36 general health total score ranges from 0 to 100, with higher scores indicating better general health.	Baseline and 12 weeks
Change in IL-6 Levels at 12 Weeks	Circulating interleukin-6 levels will be measured. Interleukin-6 is a measure of systemic inflammation.	Baseline and 12 weeks
Change is sCD14 Levels at 12 Weeks	Circulating soluble CD14 levels will be measured. Soluble CD14 is a measure of monocyte activation.	Baseline and 12 weeks
Change in sCD163 Levels at 12 Weeks	Circulating soluble CD163 levels will be measured. Soluble CD163 is a measure of monocyte/macrophage activation.	Baseline and 12 weeks
Change in CD14+CD16+ Monocytes at 12 Weeks	Circulating intermediate monocytes as defined by flow cytometric evaluation for CD14+CD16+ monocytes will be measured. CD14+CD16+ monocytes are measured by flow cytometry and indicate the pro-inflammatory subpopulation of monocytes.	Baseline and 12 weeks
Change in Insomnia Severity Index (ISI) at 12 Weeks	The Insomnia Severity Index (ISI) total score will be measured. The total scale has a minimum score of 0 and a maximum score of 28, with higher scores indicating a worse outcome.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Samir K Gupta, MD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Inflammation; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: 1R21MH127206-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will fully participate in sharing our unique datasets and associated stored samples with other interested parties once the primary analyses have been completed. This dataset will include individual-level baseline, interim visit, ancillary, procedural-based, and outcome data. Data from scored assessments (e.g., psychosocial questionnaires) will include both raw data elements (e.g., individual item responses) and summary information (e.g., total scores) where feasible. Laboratory results will also be available as individual-level results from each study visit.
• IPD Sharing Time Frame: Data will become available once the primary results are analyzed and published.
• IPD Sharing Access Criteria: Data and sample requests will be honored after submission of a short proposal that outlines an important scientific question with an appropriate statistical analysis plan that justifies the use of these datasets. In addition, the requests must also verify that confidentiality of the datasets will be ensured.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes