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Trial record 90 of 1192 for:    Adenosine

Poor Sleep and Inflammation in HIV-Infected Adults (SASH)

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ClinicalTrials.gov Identifier: NCT03848325
Recruitment Status : Not yet recruiting
First Posted : February 20, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Sanjay R Patel, University of Pittsburgh

Brief 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. 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.

Condition or disease Intervention/treatment Phase
HIV-1-infection Sleep Deprivation Inflammation Behavioral: Sleep deprivation Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Intervention 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)
Masking Description: Technicians processing biospecimens will be blinded to whether samples were collected on Day 1 or Day 2. Similarly, the assessor of brachial artery reactivity measurements will be blinded to whether ultrasound images were collected on Day 1 or Day 2.
Primary Purpose: Basic Science
Official Title: Impact of Poor Sleep on Inflammation and the Adenosine Signaling Pathway in HIV Infection
Estimated Study Start Date : December 31, 2019
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Adenosine

Arm Intervention/treatment
Experimental: Sleep deprivation
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).
Behavioral: Sleep deprivation
Eight hour opportunity for sleep followed by 24 hours of sleep deprivation.




Primary Outcome Measures :
  1. Change in soluble CD14 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in plasma concentration of soluble CD14 from baseline

  2. Change in soluble CD163 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in plasma concentration of soluble CD163 from baseline

  3. Change in IL6 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in plasma concentration of interleukin-6 from baseline


Secondary Outcome Measures :
  1. Change in flow mediated brachial artery dilation [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percent change in maximal brachial artery diameter after arterial occlusion

  2. Change in monocyte expression of IL6 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of circulating CD14+ peripheral blood mononuclear cells expressing IL-6

  3. Change in monocyte expression of TNF-alpha [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of circulating CD14+ peripheral blood mononuclear cells expressing TNF-alpha

  4. Change in CD4+ T-cell expression of HLA-DR and CD38 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of CD3+ CD4+ T-lymphocytes co-expressing HLA-DR and CD38

  5. Change in CD8+ T-cell expression of HLA-DR and CD38 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of CD3+ CD8+ T-lymphocytes co-expressing HLA-DR and CD38


Other Outcome Measures:
  1. Change in plasma adenosine [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in plasma adenosine concentration

  2. Change in plasma inosine [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in plasma inosine concentration

  3. Change in urine 3'5'-cAMP [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in urine 3'5'-cyclic adenosine monophosphate concentration normalized to creatinine

  4. Change in CD4+ T-cell expression of CD39 and/or CD73 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of CD3+ CD4+ T-lymphocytes expressing CD39 and/or CD73

  5. Change in CD8+ T-cell expression of CD39 and/or CD73 [ Time Frame: Baseline and immediately after sleep deprivation ]
    Change in percentage of CD3+ CD8+ T-lymphocytes expressing CD39 and/or CD73



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03848325


Contacts
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Contact: Shirley M Longinotti, BA 412-383-0816 sml124@pitt.edu

Locations
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United States, Pennsylvania
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15260
Contact: Shirley M Longinotti, BA    412-383-0816    sml124@pitt.edu   
Sponsors and Collaborators
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Sanjay R Patel, MD University of Pittsburgh
Principal Investigator: Bernard J Macatangay, MD University of Pittsburgh

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Responsible Party: Sanjay R Patel, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03848325     History of Changes
Other Study ID Numbers: PRO17120573
R01HL142118 ( U.S. NIH Grant/Contract )
First Posted: February 20, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanjay R Patel, University of Pittsburgh:
adenosine
Additional relevant MeSH terms:
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Adenosine
Infection
Sleep Deprivation
Inflammation
Pathologic Processes
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Mental Disorders
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action