HIV-1-infectionSASHNCT03848325
Poor Sleep and Inflammation in HIV-Infected Adults
A study testing Sleep deprivation in people with HIV-1-infection and Sleep Deprivation, run by University of Pittsburgh at 1 site in United States.
Trial summary
People living with HIV (PLWH) often have poor sleep, which may put them at a higher risk for many chronic diseases, including cardiovascular disease. One of the mechanisms by which this may occur is via chronic inflammation and endothelial dysfunction. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HIV-1-infection, Sleep Deprivation, Inflammation
- What is being tested?
- Sleep deprivation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Nov 2020to 31 Jul 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV positive
- On continuous anti-retroviral therapy regimen for at least 48 weeks
- CD4+ cell count greater than or equal to 200 cells/mm^3
Who cannot join
- Irregular or insufficient habitual sleep patterns
- Severe advanced or delayed sleep phase
- Primary sleep disorder
- Autoimmune disorder
- Use of immunosuppressant medications
- Use of medications impacting adenosine pathway
Show all 10Show fewer
- Heavy caffeine use
- Active alcohol or drug abuse
- Elevated risk of adverse health effects from sleep deprivation (e.g., bipolar disorder, epilepsy, or suicidal ideation in the past 6 months)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
About this study
Official title: Impact of Poor Sleep on Inflammation and the Adenosine Signaling Pathway in HIV Infection
People living with HIV (PLWH) often have poor sleep, which may put them at a higher risk for many chronic diseases, including cardiovascular disease. One of the mechanisms by which this may occur is via chronic inflammation and endothelial dysfunction. Adenosine plays an important role in sleep homeostasis, with levels increasing in the CSF in response to sleep deprivation and falling with sleep. Peripherally, adenosine, via its signaling pathway, plays an important role in immunoregulation by suppressing the inflammatory response. PLWH, even on antiretroviral therapy, have suppressed peripheral adenosine levels which are predictive of adverse cardiovascular outcomes. The hypothesis underlying this study is that acute sleep deprivation in PLWH does not result in a compensatory increase in extracellular adenosine and its signaling peripherally, and this failure to appropriately compensate, leads to an increase in systemic inflammation and endothelial dysfunction.
Read the detailed description
People living with HIV infection (PLWH) are known to be at higher risk of cardiovascular disease and also have a higher prevalence of poor sleep than people who do not have HIV infection. Understanding the underlying mechanisms for the elevated risk of cardiovascular disease in PLWH is important to developing novel strategies to mitigate this risk. Poor sleep has been postulated to mediate some of the elevated cardiovascular risk in PLWH given the high prevalence of poor sleep in PLWH and the epidemiologic association of poor sleep with adverse cardiovascular outcomes among people who do not have HIV infection. However, the mechanisms by which PLWH may be more sensitive to sleep loss from a cardiovascular standpoint are unclear. One potential explanation for any elevated sensitivity would be via alterations in the adenosine signaling pathway.
Changes in extracellular adenosine levels in the brain and central nervous system play an important homeostatic role in sleep-wake regulation. Sleep deprivation results in a rise in extracellular adenosine levels while sleep itself leads to a rapid decline in levels. Peripheral adenosine signaling is a central feature of immunoregulation, primarily through its effects on inflammatory cytokine expression and lymphocyte adenosine receptor expression. PLWH tend to have a suppressed level of peripheral adenosine signaling and this level of suppression predicts risk of cardiovascular disease. The purpose of this study is to explore the impact of acute sleep deprivation among PLWH on measures of inflammation and endothelial function and to assess the extent to which any changes may be explained by alterations in peripheral adenosine signaling.
The study will enroll 40 PLWH, age 18-75, who have been on ART for greater than 48 weeks. Screening with questionnaires, actigraphy and polysomnography will eliminate individuals with underlying chronic sleep abnormalities. A prior night of polysomnography in the sleep lab will also habituate subjects to sleeping while monitored in the sleep lab.
Participants will arrive in the sleep laboratory in the evening and be allowed to sleep for 8 hours timed to their usual sleep patterns. On waking, participants will provide a urine sample that will be assayed for adenosine and adenosine metabolites. Blood will be drawn to measure markers of inflammation as well as markers of activation of the peripheral adenosine signaling system. Endothelial function will be assessed using flow mediated dilation.
Participants will be kept awake for the subsequent 24 hours including the 8 hour normal sleep period. On the second morning, subjects will again provide urine and blood samples for the same bioassays described above and then undergo repeat assessment of endothelial function.
- Conditions
- HIV-1-infection, Sleep Deprivation, Inflammation
- Being tested
- Sleep deprivation
- Keywords
- adenosine
- Medical subject headings
- Sleep Deprivation, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleep deprivationBehavioural
Eight hour opportunity for sleep followed by 24 hours of sleep deprivation.
| Study group | Role | What they receive |
|---|---|---|
| Sleep deprivation | Experimental | All subjects will be provided an 8 hour opportunity for sleep (Night 1) followed by outcome assessment the next morning (Day 1). They will then be kept awake the subsequent 24 hours including Night 2, followed by outcome assessment the following morning (Day 2). Receives: Behavioral: Sleep deprivation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Soluble CD14
Plasma concentration of soluble CD14
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
Soluble CD163
Plasma concentration of soluble CD163
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
IL6
Plasma concentration of interleukin-6
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
Secondary outcomes (5)
Flow Mediated Brachial Artery Dilation
Percent change was calculated by measuring the brachial artery diameter at baseline and then the percent dilation from this baseline after release of occlusion at each time point.
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
Monocyte Expression of IL6
Percentage of circulating CD14+ peripheral blood mononuclear cells expressing interleukin-6
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
Monocyte Expression of TNF-alpha
Percentage of circulating CD14+ peripheral blood mononuclear cells expressing tumor necrosis factor-alpha
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
CD4+ T-cell Expression of HLA-DR and CD38
Percentage of CD3+ CD4+ T-lymphocytes co-expressing HLA-DR and CD38
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
CD8+ T-cell Expression of HLA-DR and CD38
Percentage of CD3+ CD8+ T-lymphocytes co-expressing HLA-DR and CD38
Measured: Baseline sleep replete state and after 24 hours of sleep deprivation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study start9 Nov 2020
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants will undergo one night of normal sleep (Night 1) followed by a subsequent night (Night 2) of sleep deprivation. Outcomes will be assessed the morning (Day 1 and Day 2) after each condition.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Sanjay R Patel, University of Pittsburgh
- Investigators
- Sanjay R Patel, MD, Principal investigator, University of PittsburghBernard J Macatangay, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03848325
- Sponsor's protocol ID
- PRO17120573
- Other IDs
- R01HL142118
- Acronym
- SASH
- Status last verified
- Nov 2023
- First submitted
- 13 Feb 2019
- Last updated
- 29 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Poor Sleep on Inflammation and the Adenosine Signaling Pathway in HIV Infection
- ClinicalTrials.gov ID
- NCT03848325
- Acronym / sponsor ID
- SASH / PRO17120573
- Conditions
- HIV-1-infection, Sleep Deprivation, Inflammation
- Keywords
- adenosine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 20 Feb 2019 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People living with HIV (PLWH) often have poor sleep, which may put them at a higher risk for many chronic diseases, including cardiovascular disease. One of the mechanisms by which this may occur is via chronic inflammation and endothelial dysfunction. Adenosine plays an important role in sleep homeostasis, with levels increasing in the CSF in response to sleep deprivation and falling with sleep. Peripherally, adenosine, via its signaling pathway, plays an important role in immunoregulation by suppressing the inflammatory response. PLWH, even on antiretroviral therapy, have suppressed peripheral adenosine levels which are predictive of adverse cardiovascular outcomes. The hypothesis underlying this study is that acute sleep deprivation in PLWH does not result in a compensatory increase in extracellular adenosine and its signaling peripherally, and this failure to appropriately compensate, leads to an increase in systemic inflammation and endothelial dysfunction.
Detailed description
People living with HIV infection (PLWH) are known to be at higher risk of cardiovascular disease and also have a higher prevalence of poor sleep than people who do not have HIV infection. Understanding the underlying mechanisms for the elevated risk of cardiovascular disease in PLWH is important to developing novel strategies to mitigate this risk. Poor sleep has been postulated to mediate some of the elevated cardiovascular risk in PLWH given the high prevalence of poor sleep in PLWH and the epidemiologic association of poor sleep with adverse cardiovascular outcomes among people who do not have HIV infection. However, the mechanisms by which PLWH may be more sensitive to sleep loss from a cardiovascular standpoint are unclear. One potential explanation for any elevated sensitivity would be via alterations in the adenosine signaling pathway.
Changes in extracellular adenosine levels in the brain and central nervous system play an important homeostatic role in sleep-wake regulation. Sleep deprivation results in a rise in extracellular adenosine levels while sleep itself leads to a rapid decline in levels. Peripheral adenosine signaling is a central feature of immunoregulation, primarily through its effects on inflammatory cytokine expression and lymphocyte adenosine receptor expression. PLWH tend to have a suppressed level of peripheral adenosine signaling and this level of suppression predicts risk of cardiovascular disease. The purpose of this study is to explore the impact of acute sleep deprivation among PLWH on measures of inflammation and endothelial function and to assess the extent to which any changes may be explained by alterations in peripheral adenosine signaling.
The study will enroll 40 PLWH, age 18-75, who have been on ART for greater than 48 weeks. Screening with questionnaires, actigraphy and polysomnography will eliminate individuals with underlying chronic sleep abnormalities. A prior night of polysomnography in the sleep lab will also habituate subjects to sleeping while monitored in the sleep lab.
Participants will arrive in the sleep laboratory in the evening and be allowed to sleep for 8 hours timed to their usual sleep patterns. On waking, participants will provide a urine sample that will be assayed for adenosine and adenosine metabolites. Blood will be drawn to measure markers of inflammation as well as markers of activation of the peripheral adenosine signaling system. Endothelial function will be assessed using flow mediated dilation.
Participants will be kept awake for the subsequent 24 hours including the 8 hour normal sleep period. On the second morning, subjects will again provide urine and blood samples for the same bioassays described above and then undergo repeat assessment of endothelial function.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants will undergo one night of normal sleep (Night 1) followed by a subsequent night (Night 2) of sleep deprivation. Outcomes will be assessed the morning (Day 1 and Day 2) after each condition.
| Arm | Type | Receives |
|---|---|---|
| Sleep deprivation | Experimental | Behavioral: Sleep deprivationAll subjects will be provided an 8 hour opportunity for sleep (Night 1) followed by outcome assessment the next morning (Day 1). They will then be kept awake the subsequent 24 hours including Night 2, followed by outcome assessment the following morning (Day 2). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HIV positive
- On continuous anti-retroviral therapy regimen for at least 48 weeks
- CD4+ cell count greater than or equal to 200 cells/mm^3
Key exclusion criteria (10 listed)
- Irregular or insufficient habitual sleep patterns
- Severe advanced or delayed sleep phase
- Primary sleep disorder
- Autoimmune disorder
- Use of immunosuppressant medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sleep deprivationEight hour opportunity for sleep followed by 24 hours of sleep deprivation. | Behavioural | Sleep deprivation |
Primary outcome
Soluble CD14
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Plasma concentration of soluble CD14
Soluble CD163
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Plasma concentration of soluble CD163
IL6
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Plasma concentration of interleukin-6
5 secondary outcomes
Flow Mediated Brachial Artery Dilation
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Monocyte Expression of IL6
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Monocyte Expression of TNF-alpha
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
CD4+ T-cell Expression of HLA-DR and CD38
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
CD8+ T-cell Expression of HLA-DR and CD38
Time frame: Baseline sleep replete state and after 24 hours of sleep deprivation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sanjay R Patel, MD principal investigator
University of Pittsburgh
Bernard J Macatangay, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sleep deprivation in people with HIV-1-infection and Sleep Deprivation, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Soluble CD14 (time frame: Baseline sleep replete state and after 24 hours of sleep deprivation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.