Clinical trial NCT04572269: Metabolomics of Obstructive Sleep Apnea
Official title: Metabolomics of Obstructive Sleep Apnea
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obstructive Sleep Apnea
Keywords: Metabolomics
Biomarker
PAP
OSA Subtype
Personalized medicine
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: University of Iceland
First posted: 2020-10-01
Enrollment: 1000
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Prospective recruitment of female and male OSA subjects n=500/site: Site #1 is University of Pennsylvania; Site #2 is University of Iceland for a total of n=1000 cases.

Brief summary: This is an R01 funded project that focuses on the utility of metabolomics as a biomarker for OSA. Aims 1 and 3 leverages banked samples previously collected from subjects with and without OSA at the University of Pennsylvania and University of Iceland. Aim 2 is a prospective study that will collect serum samples from OSA subjects at the University of Pennsylvania and the University of Iceland.

Detailed description: The primary objective of Aim 2 is to conduct a prospective observational study to evaluate the metabolomic changes in response to six months of positive airway pressure (PAP) treatment among OSA patients. Newly diagnosed OSA patients (AHI\>5) will undergo additional measurements including: accelerometer x one week (to inform the metabolomics), Type 2 home sleep test (to assist with OSA subtyping), next morning blood draw, 24-hour diet recall (to inform the metabolomics), questionnaires and PVT.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 30-75 years old
4. In good general health as evidenced by medical history and diagnosed with Obstructive Sleep Apnea (defined as AHI\>5)
5. Ability to use accelerometer, perform Type 2 sleep test at home and agree to use PAP treatment.
6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

Exclusion Criteria:

1. Current use of PAP treatment or mandibular advancement device or INSPIRE device
2. Presence of active cancer treatment or heart failure (ejection fraction \<40%)
3. Pregnancy or lactation
4. Known allergic reactions to components of the plastic (used in PAP mask)
5. Febrile illness within 2 weeks of signing consent
6. Current drug or alcohol abuse
7. Known diagnosis and treatment of diabetes because this will independently alter metabolomic results.
8. Previously drawn laboratory Hemoglobin A1C above normal range (indicative of diabetes).

Primary outcomes:
measure: Assess the utility of metabolomics to diagnose OSA and access whether these metabolomic signatures change with PAP treatment.
timeFrame: We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Secondary outcomes:
measure: Determine a metabolic signature that correlates with duration and frequency of PAP usage. This will then be correlated to subjective and objective measures of daytime sleepiness and sleep fragmentation.
timeFrame: We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Other outcomes:
measure: Evaluate whether the metabolomic response to PAP treatment is modified by degree of obesity.
timeFrame: We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
measure: Examine whether OSA symptom subtypes have a different metabolomic responses to PAP treatment.
timeFrame: We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Reykjavík
country: Iceland
facility: University of Iceland
Study officials:
affiliation: University of Pennsylvania
name: Allan Pack, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Aalim Weljie, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013 May 1;177(9):1006-14. doi: 10.1093/aje/kws342. Epub 2013 Apr 14.
citation: Lim DC, Pack AI. Obstructive Sleep Apnea: Update and Future. Annu Rev Med. 2017 Jan 14;68:99-112. doi: 10.1146/annurev-med-042915-102623. Epub 2016 Oct 5.
citation: Duran-Cantolla J, Aizpuru F, Martinez-Null C, Barbe-Illa F. Obstructive sleep apnea/hypopnea and systemic hypertension. Sleep Med Rev. 2009 Oct;13(5):323-31. doi: 10.1016/j.smrv.2008.11.001. Epub 2009 Jun 9.
citation: Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S; Sleep Heart Health Study. Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med. 2006 Apr 15;173(8):910-6. doi: 10.1164/rccm.200509-1442OC. Epub 2006 Jan 19.
citation: Li M, Hou WS, Zhang XW, Tang ZY. Obstructive sleep apnea and risk of stroke: a meta-analysis of prospective studies. Int J Cardiol. 2014 Mar 15;172(2):466-9. doi: 10.1016/j.ijcard.2013.12.230. Epub 2014 Jan 10. No abstract available.
citation: Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034-41. doi: 10.1056/NEJMoa043104.
citation: Gozal D, Jortani S, Snow AB, Kheirandish-Gozal L, Bhattacharjee R, Kim J, Capdevila OS. Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea. Am J Respir Crit Care Med. 2009 Dec 15;180(12):1253-61. doi: 10.1164/rccm.200905-0765OC. Epub 2009 Sep 24.
citation: Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5. doi: 10.1056/NEJM199304293281704.
citation: Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003 Jun;14(3):281-7. doi: 10.1097/00041433-200306000-00008.
citation: Taylor WM, Halperin ML. Effect of valine on the control of fatty acid synthesis in white adipose tissue of the rat. Can J Biochem. 1975 Oct;53(10):1054-60. doi: 10.1139/o75-145.
citation: Gehrman P, Sengupta A, Harders E, Ubeydullah E, Pack AI, Weljie A. Altered diurnal states in insomnia reflect peripheral hyperarousal and metabolic desynchrony: a preliminary study. Sleep. 2018 May 1;41(5):zsy043. doi: 10.1093/sleep/zsy043.
citation: Weljie AM, Newton J, Mercier P, Carlson E, Slupsky CM. Targeted profiling: quantitative analysis of 1H NMR metabolomics data. Anal Chem. 2006 Jul 1;78(13):4430-42. doi: 10.1021/ac060209g.
citation: Sengupta A, Krishnaiah SY, Rhoades S, Growe J, Slaff B, Venkataraman A, Olarerin-George AO, Van Dang C, Hogenesch JB, Weljie AM. Deciphering the Duality of Clock and Growth Metabolism in a Cell Autonomous System Using NMR Profiling of the Secretome. Metabolites. 2016 Jul 27;6(3):23. doi: 10.3390/metabo6030023.