HIV-related Insomnia and Inflammation

Not Applicable

Completed

Conditions: Hiv
Insomnia

Interventions: Device: SHUTi
Behavioral: Sleep Education/Hygiene

Registration Number: NCT04721067

Lead Sponsor: Indiana University

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CBT-I	SHUTi	This arm will receive internet CBT-I using SHUTi, a validated and proven therapy provided via internet in the general population.
Sleep Education/Hygiene	Sleep Education/Hygiene	This arm will receive best practices education on sleep hygiene.

Primary Outcome Measures

Name	Time	Method
Change in hsCRP Levels at 24 Weeks	Baseline and 24 weeks	Circulating high sensitivity C-reactive protein levels will be measured

Secondary Outcome Measures

Name	Time	Method
Change in IL-6 Levels at 24 Weeks	Baseline and 24 weeks	Circulating interleukin-6 levels will be measured. Interleukin-6 is a measure of systemic inflammation.
Change in CD14+CD16+ Monocytes at 24 Weeks	Baseline and 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.
Change in Hopkins Symptom Checklist (SCL-20) at 24 Weeks	Baseline and 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.
Change in Generalized Anxiety Disorder-7 (GAD-7) at 24 Weeks	Baseline and 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.
Change is sCD14 Levels at 24 Weeks	Baseline and 24 weeks	Circulating soluble CD14 levels will be measured. Soluble CD14 is a measure of monocyte activation.
Change in Pittsburgh Sleep Quality Index (PSQI) at 24 Weeks	Baseline and 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.
Change in Short Form-36 (SF-36) Health Survey and 24 Weeks	Baseline 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.
Change in sCD163 Levels at 24 Weeks	Baseline and 24 weeks	Circulating soluble CD163 levels will be measured. Soluble CD163 is a measure of monocyte/macrophage activation.
Change in hsCRP Levels at 12 Weeks	Baseline and 12 weeks	Circulating high sensitivity C-reactive protein (hsCRP) levels will be measured. hsCRP is a measure of systemic inflammation.
Change in Insomnia Severity Index (ISI) at 24 Weeks	Baseline and 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.
Change in Dysfunctional Beliefs and Attitudes About Sleep (DBAS-16) at 24 Weeks	Baseline and 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.
Change in Patient Health Questionnaire-9 (PHQ-9) at 24 Weeks	Baseline and 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.
Change in PROMIS FACIT-F Fatigue Short Form at 24 Weeks	Baseline and 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.
Change in Alcohol Use Disorders Identification Test (AUDIT) at 24 Weeks	Baseline and 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.