Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnoea Syndrome

Comparison of Oral Intake of Antioxidant Carbocysteine and Nasal Continuous Positive Airway Pressure (CPAP) for Treating in Moderate and Severe Obstructive Sleep Apnoea Syndrome Patients : a Randomized Clinical Trial

Obstructive sleep apnoea syndrome (OSAS) is characterised by repeated episodes of upper airway occlusion during sleep.It can cause cycles of hypoxia reoxygenation. And it was postulated that intermittent hypoxia seems to resemble ischemia-reperfusion.Many study suggest that ischemia-reperfusion represents an oxidative stress causing increased generation of reactive oxygen species, especially superoxide anions.It is one of the most important mechanisms of cardiovascular diseases, including hypertension, coronary artery disease and cerebrovascular accident complication with OSAS.So many individuals approve OSAS is an Oxidative Stress disease.

Continuous positive airway pressure (CPAP) is the first-line of treatment method in moderate/severe OSA.But poor adherence to CPAP treatment is very common.The failure rate with CPAP treatment is more than 50%.So we are searching a new treatment for that patients. Carbocysteine is a antioxidant.It can not only scavenges the free radicals but also replenishes glutathione(GSH)which is has double antioxidant capacity. However, Carbocysteine is cheaper than other which has double antioxidant capacity drugs,such as N-acetylcysteine.The purpose is to evaluate efficacy of oral intake of Antioxidant Carbocysteine witch can reduce oxidative stress and improve the symptom of OSAS.It recover the imbalance in the oxidant-anti-oxidant status may reduce cardiovascular abnormalities in Patients with OSAS.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnoea
• Intervention / Treatment: Drug: Carbocysteine; Device: Continuous Positive Airway Pressure

Detailed Description

OSAS patients are required to fill in questionnaire.And Inflammation biomarkers and Oxidative Stress biomarkers and ultrasonic will be tested.Then patients are randomly allocated to one of two groups. One group is treated with oral intake of Antioxidant Carbocysteine 500mg tid. The second group is treated with CPAP. After 6 weeks treatment, all patients will take the overnight polysomnogram test again, and take questionnaire, blood , ultrasonic test.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou,, Guangdong, China, 510120
      • Guangzhou Institute of Respiratory Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male in an age range of 18 to 65 years
2. Obstructive Sleep Apnoea with an Apnea Hypopnea Index (AHI) of greater than or equal to 15 confirmed by polysomnography
3. The patient is able to provide consent
4. The patient were not receiving therapy for sleep apnoea,such CPAP or surgery.

Exclusion Criteria:

1. Inability to tolerate Carbocysteine or CPAP
2. Treatment with CPAP or surgery prior to or at the time of enrolment
3. presence of active acute or chronic infection
4. Patients with unstable cardiovascular diseases (unstable angina, myocardial infarction, stroke, or transient ischemic attacks), neuromuscular diseases, chronic respiratory diseases, peripheral vascular disease
5. Using of steroidal , nonsteroidal anti-inflammatory, vasodilators ,lipid-lowering drugs,or other medications that lower oxidative stress.
6. Intake of central relevant drugs, sedatives, or other drugs which impair sleep
7. Unwilling to participate in the study
8. Participation in another clinical study in the past 4 weeks
9. Shift worker

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
Experimental: Carbocysteine; Carbocysteine , tablet ,250mg per one tablet , patients oral intake with 500mg .tid.(1500mg/day)	Drug: Carbocysteine; carbocisteine (2×250 mg, three times daily) for 6 weeks. The tablets are provided by Baiyunshan Pharmaceutical, China. patients will interviewed after 3 weeks to check their adherence to the study regimen by collecting and counting the number of remaining tablets, record adverse events, and refill study tablets for the next 3 weeks.; Other Names: S-Carboxymethylcysteine; SCMC
Active Comparator: Continuous Positive Airway Pressure; Continuous Positive Airway Pressure(CPAP),auto-CPAP(USA,Philips), patients use Nasal CPAP overnight.	Device: Continuous Positive Airway Pressure; Patients will interviewed after 3 weeks and the end of trial.We will check their compliance to device memory download , record adverse events and pressure .; Other Names: Nasal Continuous Positive Airway Pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of polysomnography (PSG) parameters after oral intake of Carbocysteine treatment	The Carbocysteine group will oral intake of Carbocysteine 500mg,tid for 6 weeks.We will examine the compliance with the drugs by Recycling the rest of the tablets.We compare the improvement of PSG parameters,such as AHI ,oxygen desaturation index(ODI),oxyhemoglobin saturation.	after 6 weeks
Daytime sleepiness(EDS) after oral intake of Carbocysteine treatment	EDS is evaluated by Epworth Sleeping Scale(ESS) grade.ESS≥9 means EDS.The higher the ESS, the more daytime sleepiness they feel.	after 6 weeks
Change of Oxidative Stress after oral intake of Carbocysteine treatment	Biomarkers is measured from venous blood.The blood is collected in the morning .After centrifugation ,the supernatant was kept at -80 degree centigrade.	after 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate efficacy of oral intake of Antioxidant Carbocysteine in comparison to Nasal continuous positive airway pressure (CPAP) treatment .	We will examine the compliance with CPAP device memory download.We will compare the two group by the PSG parameters ,ESS, and Biomarkers .	after 6 weeks treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of vascular function after oral intake of Antioxidant Carbocysteine	Vasoreactivity Testing Protocol and intima-media thickness is measured by high-resolution ultrasonography at baseline and 6 weeks after treatment.Vasoactive mediators from blood will be studied.	after 6 weeks after oral intake of Carbocysteine treatment

Collaborators and Investigators

• Sponsor: Guangzhou Institute of Respiratory Disease
• Investigators: Principal Investigator: NuoFu Zhang, professor, Guangzhou Institute of Respiratory Disease

Publications and helpful links

General Publications

• Wu K, Su X, Li G, Zhang N. Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial. PLoS One. 2016 Feb 5;11(2):e0148519. doi: 10.1371/journal.pone.0148519. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Estimate): January 7, 2015
• Last Update Submitted That Met QC Criteria: January 6, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Continuous Positive Airway Pressure; oxidative stress; Antioxidant; drug treatment; Obstructive sleep apnoea
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Anti-Infective Agents, Local; Anti-Infective Agents; Respiratory System Agents; Expectorants; Carbocysteine
• Other Study ID Numbers: IRD201319