HIV-related Insomnia and Inflammation

Indiana University30 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Hiv Insomnia

Interventions

SHUTiDEVICE

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.

Sleep Education/HygieneBEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (1)

Indiana University Infectious Diseases Research

Indianapolis, Indiana, United States

Outcomes

Primary Outcomes

Change in hsCRP Levels at 24 Weeks

Circulating high sensitivity C-reactive protein levels will be measured

Time frame: Baseline and 24 weeks

Secondary Outcomes

Change in IL-6 Levels at 24 Weeks

Circulating interleukin-6 levels will be measured. Interleukin-6 is a measure of systemic inflammation.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 12 weeks

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.

Data from ClinicalTrials.gov

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Time frame: Baseline and 24 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 24 weeks

Use of Sleep Medications at Week 12

The number of sleep medications used by each participant at Week 12

Time frame: Week 12

Use of Sleep Medications at Week 24

The number of sleep medications used by each participant at Week 24

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 12 weeks

Change in Dysfunctional Beliefs and Attitudes About Sleep (DBAS-16) at 12 Weeks

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 12 weeks

Change in PROMIS FACIT-F Fatigue Short Form at 12 Weeks

Time frame: Baseline and 12 weeks

Change in Alcohol Use Disorders Identification Test (AUDIT) at 12 Weeks

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and 12 weeks

Change in CD14+CD16+ Monocytes at 12 Weeks

Time frame: 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.

Time frame: Baseline and 12 weeks