Metabolomics of Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

— MOSA  

Official title:

Metabolomics of Obstructive Sleep Apnea

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04572269
• Other study ID #: 835027
• Status: Recruiting
• Start date: September 21, 2020
• Est. completion date: June 30, 2027

Study information

• Verified date: July 2023
• Source: University of Pennsylvania
• Contact: Kristie C Nguyen
• Phone: 215-615-4112
• Email: kristie.nguyen[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Other:
• No Intervention
This protocol does not involve an intervention of drug/device, diet, exercise or PAP compliance.

Locations

Country	Name	City	State
Iceland	University of Iceland	Reykjavík
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	University of Iceland

Countries where clinical trial is conducted

United States,  Iceland, 

References & Publications (13)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003 Jun;14(3):281-7. doi: 10.1097/00041433-200306000-00008. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate whether the metabolomic response to PAP treatment is modified by degree of obesity.	We will utilize conditional MSMs that estimate whether the effect of PAP varies with BMI.	We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Other	Examine whether OSA symptom subtypes have a different metabolomic responses to PAP treatment.	We will utilize conditional MSMs that estimate whether the effect of PAP varies across symptom subtypes.	We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Primary	Assess the utility of metabolomics to diagnose OSA and access whether these metabolomic signatures change with PAP treatment.	New OSA patients, AHI>5 will be recruited. Since this is a real-world trial, compliance of PAP usage will vary from 0 to 100%. Thus, we will be able to assess not only what metabolomic changes occur with PAP usage but also whether there is a correlation to the amount of PAP usage. Metabolomics can be used as a biomarker that correlates with duration and frequency of PAP usage. This will then be correlated to subjective and objective measures of daytime sleepiness (questionnaires + PVT) and sleep fragmentation.	We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.
Secondary	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.	We will assess whether there is a specific metabolic signature that strongly associates with PAP adherence, potentially independent of the metabolites in Outcome 1. Identifying the set of metabolites with the strongest association with PAP usage will allow us to define an objective biomarker for quantifying PAP adherence. Moreover, the pathways implicated by these biomarkers are likely to allude to certain mechanisms of response.	We anticipate prospective recruitment to be completed within 3.5 years with final analyses completed by year 4.