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Trial registered on ANZCTR


Registration number
ACTRN12616001671459
Ethics application status
Approved
Date submitted
21/11/2016
Date registered
5/12/2016
Date last updated
8/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Personalised relaxation practice to improve sleep quality in patients with chronic fatigue syndrome and depression: A Randomised Control Trial
Scientific title
Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: A Randomised Control Trial
Secondary ID [1] 290466 0
nil
Universal Trial Number (UTN)
U1111-1189-5409
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Fatigue Syndrome 300831 0
Depression 300832 0
Condition category
Condition code
Other 300657 300657 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)
Mental Health 300658 300658 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomly allocated to the intervention will be assigned to practise the relaxation method that optimizes de-arousal, determined from the results at the initial autonomic assessment. Laboratory-based autonomic measures include recordings of 3-channel electrocardiogram (ECG), respiration, sweat response and pulsatile skin blood volume. To obtain a baseline recording participants will rest in silence for 10 minutes. This is followed by the presentation of each of the three relaxation methods, order counter balanced across participants. The relaxation method which generates the greatest increase in heart rate variability (HRV), high frequency normalised units (HF nu) relative to resting baseline will be assigned to the participant for nightly practice.

This trial will utilise three different relaxation methods: ‘Guided Relaxation’, ‘Gentle Noise’, and ‘Instrumental Music’, each consisting of pre-recorded 10 minute segments. The Guided Relaxation segments are a calming voice talking through body awareness and/or progressive relaxation.The Gentle noise segments are soft, undulating white noise which sound similar to the ocean or rain. The Instrumental Music segments are calming musical pieces such as Mozart's Flute and Harp Concerto in C, K.299 2nd Movement.

Participants will have free online access to their assigned method and will be able to download the recordings to their smartphone or media device, or if preferred an MP3 player will be provided. Each participant will be provided with seven variations of their assigned method to maximise enjoyment and prevent negative effects of frequent repetition. Participants will be instructed to practice their assigned method at a minimum before bedtime every evening for 4 weeks, and may use at other times if they feel comfortable.

Participants will also keep a brief log of their sleep, activity, symptoms, and time spent practising their assigned method during this period. Weekly phone contact will be made to enhance engagement and compliance,
Intervention code [1] 296317 0
Behaviour
Intervention code [2] 296559 0
Treatment: Other
Comparator / control treatment
Participants in the monitoring only control group will complete the same assessments as the intervention group at baseline and the 4 week follow up. Control participants will be informed that they will be monitored for four weeks before receiving the intervention. They will be asked to keep a brief log of sleep, activity, and symptoms. Weekly phone contact will be made to control for placebo and Hawthorne effects. During this period they will be asked not to practise mindfulness or meditation activities. At the completion of the second laboratory assessment session (i.e. 4 weeks post randomisation) participants in the control group will be offered their personalised intervention.
Control group
Active

Outcomes
Primary outcome [1] 300113 0
Change in self-reported sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI); and daily sleep log
Timepoint [1] 300113 0
4 weeks after randomisation
Primary outcome [2] 300114 0
Change in self-reported physical and psychological health as assessed by the Somatic and Psychological Health Report (SPHERE). This questionnaire contains two validated sub-scales for somatic and psychological symptoms (the SOMA and PSYC) and also provides an overall composite score.
Timepoint [2] 300114 0
4 weeks after randomisation
Primary outcome [3] 300210 0
Change in daytime functioning as assessed by the Medical Outcomes Survey Short Form (MOS SF-36)
Timepoint [3] 300210 0
4 weeks after randomisation
Secondary outcome [1] 329089 0
Change in nocturnal autonomic functioning as monitored via nocturnal electrocardiogram (ECG).
Timepoint [1] 329089 0
4 weeks after randomisation
Secondary outcome [2] 329090 0
Change in self-reported sleep quality as assessed by the PSQI
Timepoint [2] 329090 0
8 weeks after randomisation
Secondary outcome [3] 329091 0
Change in self-reported physical and psychological health as assessed by the Somatic and Psychological Health Report (SPHERE). This questionnaire contains two validated sub-scales for somatic and psychological symptoms (the SOMA and PSYC) and also provides an overall composite score.
Timepoint [3] 329091 0
8 weeks after randomisation
Secondary outcome [4] 329092 0
Change in daytime functioning as assessed by the Medical Outcomes Survey Short Form (MOS SF-36)
Timepoint [4] 329092 0
8 weeks after randomisation
Secondary outcome [5] 329093 0
Intervention Acceptability assessed using a 3-point Likert Scale from 'not at all' to 'completely'.
Timepoint [5] 329093 0
4 weeks after randomisation
Secondary outcome [6] 329094 0
Change in self-reported psychological distress as assessed by the K-10
Timepoint [6] 329094 0
4 and 8 weeks after randomisation
Secondary outcome [7] 329877 0
Self-reported change in stress as assessed by the Perceived Stress Questionnaire (PSQ)
Timepoint [7] 329877 0
4 and 8 weeks after randomisation

Eligibility
Key inclusion criteria
Meet international diagnostic criteria for chronic fatigue syndrome; or DSM-V diagnostic criteria for depression; Normal or corrected to normal hearing; Sufficient English to complete the questionnaires and follow the guided relaxation tasks; Willingness and ability to give written informed consent and willingness to participate and comply with the longitudinal nature study.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant; Other significant illness or major diagnoses such as primary sleep disorder, heart conditions, uncontrolled diabetes, chronic infections, or psychotic disorders; Taking regular medications that affect autonomic activity including beta-blockers/anti-hypertensives; concurrently engaged in other psycho-behavioural interventions. Use of anti-depressants or the oral-contraceptive pill will be recorded but not exclusionary.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computerised permuted block randomisation, stratified by clinical condition, will be undertaken by a biostatistician prior to the commencement of the trial.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A sample size of 128 participants (64 in each arm) will be sufficient to detect improvements in fatigue (a 3-point reduction in SOMA score), psychological distress (a 5-point reduction in K10 score), and sleep quality (reduction in PSQI of 2) in the intervention arm, with 80% power, and a Bonferroni-adjusted significance level of 0.013 allowing for multiple comparisons. This conservative estimate will allow for a drop-out rate of up to 10%. Estimates of effect size are based on preliminary data using this protocol, utilising standard deviations (SOMA SD = 2.7; PSQI SD = 3.2; K10 SD = 5.5) from published data in these patient group. The outcome variables will be analysed using regression modelling, with treatment arm (intervention / control) included as a dichotomous between-subjects variable, and baseline values of the variable included as a within-subjects covariate (to control for chance differences between arms at baseline).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 294881 0
Charities/Societies/Foundations
Name [1] 294881 0
The Judith Jane Mason & Harold Stannett Williams Memorial Foundation
Address [1] 294881 0
Equity Trustees Wealth Services Limited
Level 2, 575 Bourke St, Melbourne, Vic, 3000
Country [1] 294881 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW Australia, High Street, Kensington, NSW, 2052
Country
Australia
Secondary sponsor category [1] 293921 0
None
Name [1] 293921 0
Address [1] 293921 0
Country [1] 293921 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296287 0
UNSW Human Research Ethics Committee
Ethics committee address [1] 296287 0
UNSW, Level 3 Rupert Myers Building (South Wing), Kensington, NSW, 2052
Ethics committee country [1] 296287 0
Australia
Date submitted for ethics approval [1] 296287 0
22/11/2016
Approval date [1] 296287 0
16/12/2016
Ethics approval number [1] 296287 0
HC16953

Summary
Brief summary
Debilitating fatigue; unrefreshing sleep and poor daytime functioning are core features of many neuropsychiatric conditions including chronic fatigue syndrome (CFS) and major depression. Understanding of the aetiologies of these conditions is still incomplete and symptom management strategies have only limited efficacy.
Accumulating evidence suggests that abnormalities in the function of the autonomic nervous system play a role in the sleep disturbance and chronic fatigue in these conditions. In particular, autonomic activity is characterized by neural hyper-vigilance and a marked loss of parasympathetic, vagus nerve activity that persist even during sleep. Measures of beat-to-beat heart rate variability (HRV) provide well-established, reliable indices of autonomic functioning, which consistently correlate with the severity and outcome of a spectrum of fatiguing disorders, including autoimmune and cardiovascular disease, chronic pain, depression, and CFS . For example, low HRV was repeatedly found to be a strong correlate of unrefreshing sleep, daytime fatigue and cognitive impairment in CFS.
Mindfulness-based stress reduction and relaxation methods are increasingly utilised with the aim to restore autonomic balance. It is believed that the beneficial effects of these approaches are mediated via their impact on neural circuits involved in self-regulation, and on key stress-response pathways. However, individuals can have very different responses to different relaxations methods; and recent analyses revealed that some patients do not respond optimally to some.
The main of the current study is to conduct a randomized control trial (RCT) to determine the efficacy and specific benefits of a 4 week personalised relaxation intervention, pre-tested to optimise the individuals' own HRV. Subjective health outcomes and parasympathetic autonomic activity (indexed by HRV) in patients with CFS and depression will be compared to a ‘monitoring only’ control condition. We anticipate that daily practice of a personalised relaxation method before sleep will be substantively more effective in improving sleep quality, daytime fatigue and functioning in both patient groups compared to treatment as usual with symptom monitoring. We further anticipate that restoration of HRV will contribute to positive health outcomes. The findings from this research will facilitate a better understanding of the pathophysiological mechanisms operating in chronic fatigue conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67266 0
A/Prof Ute Vollmer-Conna
Address 67266 0
Level 1, 30 Botany Street,UNSW, Sydney, NSW, 2052
Country 67266 0
Australia
Phone 67266 0
+610293852945
Fax 67266 0
Email 67266 0
ute@unsw.edu.au
Contact person for public queries
Name 67267 0
A/Prof Ute Vollmer-Conna
Address 67267 0
Level 1, 30 Botany Street,UNSW, Sydney, NSW, 2052
Country 67267 0
Australia
Phone 67267 0
+610293852942
Fax 67267 0
Email 67267 0
human.behav@unsw.edu.au
Contact person for scientific queries
Name 67268 0
A/Prof Ute Vollmer-Conna
Address 67268 0
Level 1, 30 Botany Street,UNSW, Sydney, NSW, 2052
Country 67268 0
Australia
Phone 67268 0
+610293852945
Fax 67268 0
Email 67268 0
ute@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results