Poor Sleep and Inflammation in HIV-Infected Adults
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Insomnia Sleep Studies, Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 2/22/2019 |
| Start Date: | June 1, 2019 |
| End Date: | July 31, 2022 |
| Contact: | Shirley M Longinotti, BA |
| Email: | sml124@pitt.edu |
| Phone: | 412-383-0816 |
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.
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.
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.
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.
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
We found this trial at
1
site
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Phone: 412-383-0816
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
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