SPA Therapy in the Treatment of Sleep Apnea Syndrome (THERMA-SAS)

Impact of 3-week SPA Therapy on Sleep Apnea in Patients With Obstructive Sleep Apnea Syndrome and Chronic Venous Insufficiency: A Randomized, Controlled Study

The purpose of this study is to determine whether 3-week of SPA therapy improves sleep apnea in patients with chronic venous insufficiency and concomitant Obstructive Sleep Apnea Syndrome (OSAS).

Study Overview

• Status: Withdrawn
• Conditions: Obstructive Sleep Apnea Syndrome; Chronic Venous Insufficiency
• Intervention / Treatment: Other: 3-week immediate SPA treatment; Other: 3-week late SPA treatment

Detailed Description

Obstructive Sleep Apnea Syndrome (OSAS), characterized by repetitive episodes of partial or complete upper airway (UA) obstruction, is highly prevalent in the general population (2% in women, 4% in men). OSAS is associated with hypersomnolence and it increases the risk of cardiovascular morbidity and mortality. Its pathogenesis is largely multifactorial. In patients with chronic venous insufficiency, fluid retention contributes to this pathogenesis: during the day, fluid accumulates in the legs due to gravity ; during sleep in recumbent position, this accumulated fluid redistributes rostrally in the neck and causes upper airway narrowing and predisposes to OSAS.

The hypothesis is that a comprehensive treatment program for chronic venous insufficiency (SPA therapy) would reduce sleep apnea in patients with chronic venous insufficiency and concomitant sleep apnea Syndrome.

The objective is to assess the efficacy of a 3-week SPA therapy on attenuation of sleep apnea in this population of patients.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Annecy, France
    • Medical pratice (angiology)
  • Bourgoin Jallieu, France
    • Medical practice (angiology)
  • Castelnau Le Lez, France
    • Medical practice (angiology)
  • Grenoble, France
    • University Hospital Grenoble
  • Grenoble, France, 38000
    • University Hospital Grenoble
  • Grenoble, France
    • Medical pratice (angiology)
  • Montpellier, France
    • Clinic Beau Soleil
  • Tarbes, France
    • Medical pratice (angiology)
  • Valence, France
    • Medical practice (angiology)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with Chronic Venous Insufficiency with oedema (CEAP clinical classes C3 to C5) and concomitant Sleep Apnea Syndrome (AHI > 15 events/hour)
• Patient in stable state (no change in medical treatment and no hospitalization for respiratory, cardiac or metabolic event in the 2 months preceding inclusion)
• Patient available for a program of 3-week SPA Therapy

Exclusion Criteria:

• Patient with no social insurance
• Pregnant and nursing woman
• Patient detained by judicial order
• Patient with contra-indication to SPA therapy
• Patient with chronic venous insufficiency < CEAP C3 or CEAP C6
• Patient already treated by class IV compression stockings for severe veinolymphatic insufficiency
• Patient already treated for sleep apnea
• Patient who have already benefited of SPA therapy (any type) within 9 months before the enrollment
• Patient with severe comorbidities
• Patient who could not respect the constraints related to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate SPA treatment; 3-week immediate SPA treatment (soon after randomization)	Other: 3-week immediate SPA treatment; a comprehensive program soon after randomization including sessions of balneotherapy, diet information, exercise training. The most adapted to the concerned pathology and common to all SPA resorts (walk in a specially pool, whirlpool bath with automatic air and water massages cycles, massages shower...); Other Names: Immediate SPA treatment
Sham Comparator: Late SPA treatment; 3-week late SPA treatment (soon after primary endpoint at 4 1/2 months visit)	Other: 3-week late SPA treatment; a comprehensive program after 4.5 months, including sessions of balneotherapy, diet information, exercise training. The most adapted to the concerned pathology and common to all SPA resorts (walk in a specially pool, whirlpool bath with automatic air and water massages cycles, massages shower...); Other Names: Late SPA treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea-Hypopnea Index (AHI)	Variation in AHI according to the allocation group	4.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific Quality of life	Variation in the scores of CIVIQ 20 according to the allocation group (Specific quality of life scale for venous insufficiency)	4.5 months
Global Quality of life	Variation in the score of EUROQUOL according to the allocation group (Global quality of life scale)	4.5 months
severity of sleep apnea	Variation of AHI according to the severity of sleep apnea at inclusion. Moderate sleep apnea (AHI <30) vs Severe Sleep apnea (AHI >30) at inclusion	4.5 months
Nocturnal hypoxemia	Nocturnal hypoxemia is assessed by mean SpO2 and time spent with SpO2<90%	4.5 months
Clinically significant improvement of OSAS	Clinically significant improvement is defined with a reduction in AHI by 50% or more and a reduction in oxygen desaturation index by 50% or more	4.5 months
Sleep duration	Mean sleep duration is assessed by actigraphy over a period of 7 days.	4.5 months
Quality of Sleep	Quality of sleep is assessed by Quebec Quality of life Questionnaire	4.5 months
Daytime sleepiness	Sleepiness is assessed by Epworth sleepiness scale	4.5 months
Variation of interstitial fluid	bioimpedance is used to measure interstitial fluid	4.5 months
Long term efficacy	Long term efficacy is measured by nocturnal respiratory polygraphy only in patients who are not treated by CPAP	1 year
Venous insufficiency classification	Variation of venous insufficiency is assessed by CEAP classification	1 year
Venous insufficiency variation	Variation of venous insufficiency is assessed by Villalta score	1 year
Venous insufficiency examination	Variation of venous insufficiency is assessed by leg circumferences	1 year
long term effect of the SPA treatment on primary outcome	confirmation of the long term effect of the SPA treatment at 1 year for the control group. Primary outcome evolution between 4.5 months and 12 months (evolution of AHI)	1 year
long term effect of the SPA treatment on specific quality of life	confirmation of the long term effect of the SPA treatment at 1 year for the control group. Evolution between 4.5 months and 12 months of specific quality of life with CIVIQ 20 scale	1 year
long term effect of the SPA treatment on global quality of life	confirmation of the long term effect of the SPA treatment at 1 year for the control group. Evolution between 4.5 months and 12 months of global quality of life with EUROQUOL Scale	1 year
long term effect of the SPA treatment on venous insufficiency	confirmation of the long term effect of the SPA treatment at 1 year for the control group. Evolution between 4.5 months and 12 months of venous insufficiency	1 year
long term effect of the SPA treatment on specific treatment of OSAS	confirmation of the long term effect of the SPA treatment at 1 year for the control group. Evolution between 4.5 months and 12 months. The long term effect will be confirmed if patients did not require a specific treatment of OSAS (for example CPAP (Continuous Positive Airway Pressure).	1 year
benefit for patients with first SPA treatment	stratification at randomization (first SPA treatment or not) to evaluate a higher benefit (variation of Apnea-Hypopnea Index (AHI)) for patients with first SPA treatment. Comparison of patients with first SPA treatment or not on primary outcome according to the allocation group.	4.5 months

Collaborators and Investigators

• Sponsor: Association Francaise pour la Recherche Thermale
• Collaborators: University Hospital, Grenoble; Floralis
• Investigators: Principal Investigator: Jean Louis PEPIN, MD, University Hospital, Grenoble

Publications and helpful links

General Publications

• Redolfi S, Arnulf I, Pottier M, Lajou J, Koskas I, Bradley TD, Similowski T. Attenuation of obstructive sleep apnea by compression stockings in subjects with venous insufficiency. Am J Respir Crit Care Med. 2011 Nov 1;184(9):1062-6. doi: 10.1164/rccm.201102-0350OC.
• Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008 Feb 15;5(2):136-43. doi: 10.1513/pats.200709-155MG.
• Caffo B, Diener-West M, Punjabi NM, Samet J. A novel approach to prediction of mild obstructive sleep disordered breathing in a population-based sample: the Sleep Heart Health Study. Sleep. 2010 Dec;33(12):1641-8. doi: 10.1093/sleep/33.12.1641.
• Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009 Aug;108(5):246-9.
• Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25;365(9464):1046-53. doi: 10.1016/S0140-6736(05)71141-7.
• Monahan K, Storfer-Isser A, Mehra R, Shahar E, Mittleman M, Rottman J, Punjabi N, Sanders M, Quan SF, Resnick H, Redline S. Triggering of nocturnal arrhythmias by sleep-disordered breathing events. J Am Coll Cardiol. 2009 Nov 3;54(19):1797-804. doi: 10.1016/j.jacc.2009.06.038.
• Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378-84. doi: 10.1056/NEJM200005113421901.
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• Levy P, Pepin JL, Dematteis M. Pharyngeal neuropathy in obstructive sleep apnea: where are we going? Am J Respir Crit Care Med. 2012 Feb 1;185(3):241-3. doi: 10.1164/rccm.201111-1992ED. No abstract available.
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• Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, Parker JD, Bradley TD. Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail. 2009 May;15(4):279-85. doi: 10.1016/j.cardfail.2008.11.015. Epub 2009 Jan 21.
• de Oliveira Rodrigues CJ, Marson O, Tufic S, Kohlmann O Jr, Guimaraes SM, Togeiro P, Ribeiro AB, Tavares A. Relationship among end-stage renal disease, hypertension, and sleep apnea in nondiabetic dialysis patients. Am J Hypertens. 2005 Feb;18(2 Pt 1):152-7. doi: 10.1016/j.amjhyper.2004.08.028.
• Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, Leung RS, Bradley TD. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001 Dec;19(12):2271-7. doi: 10.1097/00004872-200112000-00022.
• Yumino D, Redolfi S, Ruttanaumpawan P, Su MC, Smith S, Newton GE, Mak S, Bradley TD. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation. 2010 Apr 13;121(14):1598-605. doi: 10.1161/CIRCULATIONAHA.109.902452. Epub 2010 Mar 29.
• Friedman O, Bradley TD, Chan CT, Parkes R, Logan AG. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010 Dec;56(6):1077-82. doi: 10.1161/HYPERTENSIONAHA.110.154427. Epub 2010 Nov 8.
• Elias RM, Bradley TD, Kasai T, Motwani SS, Chan CT. Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea. Nephrol Dial Transplant. 2012 Apr;27(4):1569-73. doi: 10.1093/ndt/gfr605. Epub 2011 Nov 5.
• Rapoport DM, Garay SM, Epstein H, Goldring RM. Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome". Chest. 1986 May;89(5):627-35. doi: 10.1378/chest.89.5.627.
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• Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007 Apr 23;167(8):757-64. doi: 10.1001/archinte.167.8.757.
• Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, Barbe F, Vicente E, Wei Y, Nieto FJ, Jelic S. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012 May 23;307(20):2169-76. doi: 10.1001/jama.2012.3418.
• Sharma SK, Agrawal S, Damodaran D, Sreenivas V, Kadhiravan T, Lakshmy R, Jagia P, Kumar A. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med. 2011 Dec 15;365(24):2277-86. doi: 10.1056/NEJMoa1103944.
• Papandreou C, Schiza SE, Bouloukaki I, Hatzis CM, Kafatos AG, Siafakas NM, Tzanakis NE. Effect of Mediterranean diet versus prudent diet combined with physical activity on OSAS: a randomised trial. Eur Respir J. 2012 Jun;39(6):1398-404. doi: 10.1183/09031936.00103411. Epub 2011 Oct 27.
• Kline CE, Crowley EP, Ewing GB, Burch JB, Blair SN, Durstine JL, Davis JM, Youngstedt SD. The effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trial. Sleep. 2011 Dec 1;34(12):1631-40. doi: 10.5665/sleep.1422.
• Mirrakhimov AE. Physical exercise related improvement in obstructive sleep apnea. Look for the rostral fluid shift. Med Hypotheses. 2013 Feb;80(2):125-8. doi: 10.1016/j.mehy.2012.11.007. Epub 2012 Dec 3.
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• Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, Woodson BT, Van de Heyning PH, Goetting MG, Vanderveken OM, Feldman N, Knaack L, Strohl KP; STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014 Jan 9;370(2):139-49. doi: 10.1056/NEJMoa1308659.
• Chan AS, Sutherland K, Schwab RJ, Zeng B, Petocz P, Lee RW, Darendeliler MA, Cistulli PA. The effect of mandibular advancement on upper airway structure in obstructive sleep apnoea. Thorax. 2010 Aug;65(8):726-32. doi: 10.1136/thx.2009.131094.
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Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: September 23, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Actual): June 29, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: sleep apnea; Venous Insufficiency; SPA treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Apnea; Venous Insufficiency
• Other Study ID Numbers: THERMA SAS