Clinical trial NCT02939586: The Effect of Haemodialysis in Sleep Apnoea
Official title: A Cross-sectional, Randomised-controlled Study to Investigate the Effect of HDF vs HD in Sleep Apnoea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Apnoea
Renal Failure
End Stage Kidney Disease
Sleep Disturbance
Sleep Disorders
Sleep
Keywords: Sleep, Sleep apnoea, Haemodialysis, Haemodiafiltration, end stage kidney disease
Lead sponsor: John Hunter Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Newcastle University
name: Hunter Medical Research Institute
First posted: 2016-10-20
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: eligible participants from stage 1 screening will be invited to participate in stage 2 RCT. participants will be randomly assigned to either HD or HDF for 2 months, 1 month wash-our period and cross-over to the other treatment for another 2 months. The total trial period will be 5 months.
Primary purpose: TREATMENT

Brief summary: Sleep disturbance is a significant issue in people undergoing dialysis. More than 80% of haemodialysis patients complain of difficulty sleeping. Inadequate sleep can cause poor daytime function and increased risk of motor vehicle incidents.

One of the common reasons for sleep disturbance in dialysis patients is sleep apnoea. Sleep apnoea involves pauses in breathing that occur during sleep. Each pause can last only a few seconds or minutes. Severe sleep apnoea reduces oxygen supply and increases risk of heart attack and stroke, which are the leading causes of death in dialysis patients.

In this project, the investigators will examine how a change of dialysis treatment might improve sleep. This project will first identify patients at risk of sleep disturbance using surveys and a subsequent sleep study. The investigators will then test different dialysis models to see the effect of dialysis treatment on sleep apnoea. The aim is to find a dialysis model that works better for patients with sleep apnoea.

Detailed description: Sleep Problem in Dialysis Patients Sleep apnoea is a significant issue in patients with end stage kidney disease. Evidence suggests that up to 80% of dialysis patients have sleep apnoea \[1\], yet the standard haemodialysis treatment does not improve the symptoms of sleep disturbance in most patients \[2\].

Sleep disturbance is specifically associated with poor quality of life (QoL) \[4\]; decreased mental and physical function, and adversely impact survival \[5-7\]. Recent data also suggest that the low oxygen state resulting from sleep apnoea can exaggerate the deterioration of kidney function and increase risk of high blood pressure, cardiovascular abnormality and overall death rates \[8\]. Despite the significance of sleep apnoea, it is acknowledged that there is insufficient evidence for clinicians to manage this common symptom burden in the dialysis population \[9\]; and patients who receive maintenance dialysis today still experience poor QoL and worse survival rates compared with most common cancer sufferers \[10\].

Knowledge Gap It is believed that the mechanism of sleep apnoea in dialysis patients are related to overactive chemoreceptors, which cause destabilisation of the respiratory drive and periodic breathing during the night \[13\]. Since the chemoreceptors can be triggered by inflammatory blood toxins, which accumulate in kidney failure \[14\], it is proposed that better clearance of these molecules can improve symptoms and outcomes of sleep apnoea. These molecules are poorly removed by standard haemodialysis \[15\] and are thought to cause the symptomatic effects of poor kidney function and inflammation, which are associated with poor sleep quality \[16\].

Better dialysis treatment may play an important role in the management of sleep apnoea. Previous studies have suggested that sleep apnoea may be improved by nocturnal dialysis; an intensive treatment which patients undergo at home, during sleep, for 8-10 hours every night. It provides better blood purification, compared with standard haemodialysis treatment. However, nocturnal dialysis is a home therapy which is not viable for the majority of haemodialysis patients who require care in a clinical setting. There is clearly a need to explore the effectiveness of dialysis treatment on sleep apnoea using a different dialysis model.

Modern dialysis technology, such as Haemodiafiltration (HDF), allows for better removal of toxic molecules such as beta 2 microglobulin (B2M) and C-Reactive protein (CRP), than standard haemodialysis treatment, and may offer the benefits of nocturnal dialysis to all dialysis patients. No one has examined the effect of HDF on sleep apnoea in haemodialysis patients, and the investigators will answer this question in this study.

Research Aims

1. To determine the prevalence of sleep apnoea in the local dialysis population using a validated questionnaire and sleep study. Although sleep apnoea is recognised as common in the dialysis population, there is a need to reproduce this data in the context of local dialysis services to accurately identify affected patients
2. To examine the effect of HDF compared conventional haemodialysis on health status and sleep quality in patients with sleep apnoea, using a randomised cross-over trial (RCT)
3. To determine if the clearance of middle-sized uraemic toxins improves symptoms of sleep apnoea. The middle-sized molecules to be assessed in this study include C-Reactive protein (CRP), beta 2-microglobulin (β2M), tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8), which are the serum inflammatory markers that are commonly found in patients with obstructive sleep apnoea.

Eligibility criteria: Inclusion criteria

* Individuals receiving maintenance haemodialysis under the care of Nephrology Department, John Hunter Hospital \& Manning Base Hospital
* Have received dialysis for more than 3 months.
* Greater than 18 years of age
* Able to provide informed consent
* Satisfactory written and spoken English language skills
* AHI score between 15-29 or above 30 if the participant a. declines sleep apnoea treatment after discussing with their physician, b. would like to be involved in the trial whilst awaiting an appointment in the sleep clinic.

Exclusion criteria

* Acute dialysis or acutely unwell patients
* Home dialysis patients
* Unable to participate in the study in the opinion of the participant's primary Nephrologist or due to language barrier or cognitive impairment.
* Already on treatment for sleep-disordered breathing
* Woman who are pregnant

Primary outcomes:
measure: Severity of Sleep Apnea measured by Apnea-hypopnea index
timeFrame: 18 months
Secondary outcomes:
measure: Patient-reported sleep quality measured by PSQI
timeFrame: 18 months
measure: Patient-reported daytime sleepiness measured by ESS
timeFrame: 18 months
measure: Overall quality of life measured by KDQoL-36
timeFrame: 18 months
measure: The different concentration of inflammatory biomarkers (CRP, β2M, TNF-α, IL-6 and IL-8) during HDF period vs HD period, and the correlation to AHI, and overall sleep quality and quality of life.
timeFrame: 18 months
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
Study officials:
affiliation: Academic Clinician/University of Newcastle
name: Vanessa McDonald, PhD
role: PRINCIPAL_INVESTIGATOR
References: