HIV-related Insomnia and Inflammation

• ClinicalTrials.gov Identifier: NCT04721067
• Recruitment Status: Recruiting
• First Posted: January 22, 2021
• Last Update Posted: October 13, 2022
• Sponsor: Indiana University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Samir K. Gupta, MD, Indiana University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hiv; Insomnia	Device: SHUTi; Behavioral: Sleep Education/Hygiene	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: The study outcomes will be analyzed and compared by blinded investigators and statisticians.
• Primary Purpose: Treatment
• Official Title: Treating Insomnia to Reduce Inflammation in HIV
• Actual Study Start Date: December 2, 2021
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in hsCRP levels at 24 weeks [ Time Frame: Baseline and 24 weeks ]
   Circulating high sensitivity C-reactive protein levels will be measured

Secondary Outcome Measures :

1. Change is IL-6 levels at 12 and 24 weeks [ Time Frame: Baseline, 12 and 24 weeks ]
   Circulating interleukin-6 levels will be measured
2. Change is sCD14 levels at 12 and 24 weeks [ Time Frame: Baseline, 12 and 24 weeks ]
   Circulating soluble CD14 levels will be measured
3. Change in sCD163 levels at 12 and 24 weeks [ Time Frame: Baseline,12 and 24 weeks ]
   Circulating soluble CD163 levels will be measured
4. Change in CD14+CD16+ monocytes at 12 and 24 weeks [ Time Frame: Baseline,12 and 24 weeks ]
   Circulating intermediate monocytes as defined by flow cytometric evaluation for CD14+CD16+ monocytes will be measured
5. Change in hsCRP levels at 12 weeks [ Time Frame: Baseline and 12 weeks ]
   Circulating high sensitivity C-reactive protein levels will be measured
6. Change in Insomnia Severity Index (ISI) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
   ISI questionnaire scores will be measured
7. Change in Pittsburgh Sleep Quality Index (PSQI) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
   PSQI questionnaire scores will be measured
8. Change in Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
   DBAS-16 questionnaire scores will be measured
9. Change in Patient Health Questionnaire-9 (PHQ-9) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
   PHQ-9 questionnaire scores will be measured
10. Change in Hopkins Symptom Checklist (SCL-20) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    SCL-20 questionnaire scores will be measured
11. Change in Generalized Anxiety Disorder-7 (GAD-7) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    GAD-7 questionnaire scores will be measured
12. Change in PROMIS Fatigue Short Form at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    PROMIS questionnaire scores will be measured
13. Change in Alcohol Use Disorders Identification Test (AUDIT) at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    AUDIT questionnaire scores will be measured
14. Change in Short Form-36 (SF-36) Health Survey at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    SF-36 questionnaire scores will be measured
15. Change in sleep medication use at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    Concomitant medications for sleep will be recorded
16. Change in insomnia treatment satisfaction at 12 and 24 weeks [ Time Frame: Baseline, 12, and 24 weeks ]
    Insomnia treatment satisfaction scores will be measured

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Danielle Grounds, RVT; 317-278-0255; diground@iu.edu

Contact: Lora Fortenberry, NP; 317-274-8453; lfortenb@iu.edu

Locations

United States, Indiana

Indiana University Infectious Diseases Research; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Danielle Grounds

Contact: Samir Gupta

Sponsors and Collaborators

Indiana University

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Samir K Gupta, MD; Indiana University School of Medicine

  Study Documents (Full-Text)

Documents provided by Samir K. Gupta, MD, Indiana University:

Study Protocol  [PDF] July 29, 2022

Informed Consent Form  [PDF] July 29, 2022

More Information

• Responsible Party: Samir K. Gupta, MD, Professor of Medicine, Indiana University
• ClinicalTrials.gov Identifier: NCT04721067
• Other Study ID Numbers: 1R21MH127206-01 ( U.S. NIH Grant/Contract ); 1R21MH127206-01 ( U.S. NIH Grant/Contract )
• First Posted: January 22, 2021
• Last Update Posted: October 13, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data will become available once the primary results are analyzed and published.
• 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.

• 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

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Inflammation; Pathologic Processes; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders