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Trial registered on ANZCTR


Registration number
ACTRN12621000285853
Ethics application status
Approved
Date submitted
8/01/2021
Date registered
16/03/2021
Date last updated
16/03/2021
Date data sharing statement initially provided
16/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Inspiratory Muscle Training on Blood Pressure in patients with Obstructive Sleep Apnea and Hypertension
Scientific title
Inspiratory Muscle Training in patients with Obstructive Sleep Apnea and Hypertension
Secondary ID [1] 303115 0
Nil known
Universal Trial Number (UTN)
U1111-1263-5458
Trial acronym
SYSTOLE (inSpiratorY muScle Training Obstructive sLeep apnEa)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnea 320212 0
Hypertension 320213 0
Condition category
Condition code
Respiratory 318149 318149 0 0
Sleep apnoea
Cardiovascular 318150 318150 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigators:
The study investigator: A PhD candidate who has been trained to use the VMax machine and undertake the respiratory function tests required to calibrate the IMT device. The study investigator will also demonstrate/ train study participants on how to use their IMT devices. In addition, the study investigator has also been trained to perform all autonomic and hemodynamic tests in this study.

Sleep Physician: The Principal Investigator is a sleep physician who will be responsible for the recruitment of suitable study candidates.

Recruitment:
Participants presenting to a sleep clinic (Royal North Shore Hospital) will be approached for recruitment by the treating sleep physician. The inclusion criteria dictate that all patients selected for recruitment will have a history of hypertension and OSA.

Visits: All face-to-face study visits will take place at The Charles Perkins Centre, Royal Prince Alfred Hospital Clinic, University of Sydney

Study visits:
Visit 1 (5 minutes): Participants to provide formal written consent before they are randomised to receive High or low-Intensity Inspiratory Muscle Training (IMT) using Threshold IMT (Philips Respironics, Sussex, UK).

Visit 2 (30 minutes): A face-to-face visit with the study investigator will be undertaken where the participant will be set-up with 24-hour ambulatory blood pressure (15 minutes). They will return this device the following day. An e-mail will be sent with a link to Questionnaires (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and SF-36 Short Form Health Survey) that will require completion the same night at home (15 minutes).

Visit 3 (1.5 hour): The morning following visit 2 the blood pressure monitor will be returned. The study investigator will perform respiratory function tests on the participant to determine maximal inspiratory pressure and calibrate the IMT device accordingly.

Baseline measures to be undertaken: Autonomic and haemodynamic tests (electrocardiography, finger photoplethysmography, and pulse wave analysis).

Participants will be sent home with their newly calibrated IMT device. They will be shown how to use the device by the study investigator. Participants will be prescribed training for 5 minutes per day/ 7 days a week for 6 weeks. At the 3-week mark, participants will be asked to return to the clinic for visit 4. Compliance will be assessed subjectively using a device use log. Participants will be contacted by phone each week by the study investigator to encourage compliance and assist with any issues related to the study.

Visit 4 (30 minutes): respiratory function tests and device recalibration. Participants will use these settings for the remainder of the training program.

Visit 5 (30 minutes): After 6 weeks of treatment, participants will return for a face-to-face visit where a 24-hour ambulatory blood pressure monitor will be set up (15 minutes) and questionnaires will be completed that day. An additional questionnaire assessing the participant's response to treatment will also be completed (15 minutes).

Visit 6 (1.5 hours): Participants will return the next morning for a face-to-face visit. The 24-hr blood pressure monitor will be returned. Final autonomic and respiratory function tests will be completed. Participants will be sent home to repeat the final sleep study and the device will be returned at their earliest convenience.

IMT: This device acts as an inspiratory muscle trainer that will help increase respiratory muscle strength and endurance through conditioning. Participants breathe into a mouthpiece which is connected to the inspiratory muscle trainer. The device contains a pressure loaded inspiratory valve and an unloaded expiratory flap valve. This allows for resistance upon inspiration only and can be manually shifted to provide higher or lower resistance.
Participants are randomised to receive low or high resistance IMT.

High resistance:
Devices will be calibrated to 75% of the maximal inspiratory mouth pressure for each participant.

Low resistance:
Devices will be calibrated to 15% of the maximal inspiratory mouth pressure for each participant.
Intervention code [1] 319415 0
Treatment: Devices
Intervention code [2] 319750 0
Treatment: Other
Comparator / control treatment
Arm 2:
Devices will be calibrated to 15% of the maximal inspiratory mouth pressure for each participant.
Control group
Dose comparison

Outcomes
Primary outcome [1] 326139 0
Blood pressure:
This outcome will be measured using a sphygmomanometer. The Oscar 2™ Ambulatory Blood Pressure Monitor from SunTech Medical® will be used to assess 24-hour blood pressure. This is the gold standard in 24-hour ambulatory blood pressure monitoring (ABPM).
Timepoint [1] 326139 0
Before the commencement of treatment (Visit 2, Week 1) and upon completion of the trial period (Visit 5, Week 6)
Secondary outcome [1] 390228 0
Autonomic function:
Continuous blood pressure waveform and ECG will be recorded for 10 minutes in the supine position, using the Human Non-Invasive Blood Pressure System (NIBP). The Human NIBP system accurately determines beat-to-beat blood pressure, enabling assessment of autonomic cardiovascular control such as spontaneous baroreflex function, and blood pressure variability. The human NIBP system operates via a photoplethysmographic cuff (blood pressure cuff with an infrared sensitive photocell), a pressure manometer, an automatic unit for cuff inflation, a 3-lead ECG and a monitor for the digital display of systolic blood pressure, diastolic blood pressure and heart rate. The finger cuff is designed for the adult finger with an automated calibration device attached to the cuff which maintains constant transmural pressure on the finger. Therefore, assessment of autonomic function will be derived from the recorded blood pressure. An ECG will be undertaken simultaneously which will be used to derive heart rate variability.
Timepoint [1] 390228 0
Before the commencement of treatment (Visit 2, Week 1) and upon completion of the trial period (Visit 5, Week 6)
Secondary outcome [2] 390229 0
Pulse Wave Velocity:
The SphygmoCor XCEL system enables the non-invasive measurement of pulse wave velocity of the blood pressure waveform travelling between two arterial sites. Measurements will be performed by recording pressure waveforms at the carotid artery followed by the femoral artery using a tonometer pressure sensor along with ECG signal recorded simultaneously. The SphygmoCor XCEL system also enables us to assess peripheral arterial stiffness as an output using the augmentation index.
Timepoint [2] 390229 0
Before the commencement of treatment (Visit 2, Week 1) and upon completion of the trial period (Visit 5, Week 6)

Eligibility
Key inclusion criteria
• Participants presenting to a sleep clinic (Royal North Shore Hospital)
• Adults (male and female)
• Willingness to undergo IMT for 6 weeks.
• Willingness to provide informed consent and willingness to participate and comply with the study requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous or current OSA treatment.
• Women who are lactating or pregnant
• Driving risk, report an accident (or near miss accident) because of sleepiness in the last 6 months
• Need for immediate therapy as assessed by treating sleep physician.
• Patients with a history of psychological illness or conditions such as to interfere with the patient’s ability to understand the requirements of the study
• Previous history of pneumothorax
• Burst eardrum or other conditions of the eardrum
• Unstable asthma with an abnormally low perception of dyspnoea
• Coexisting sleep disorder, shift work, regular use of sedatives or narcotics, pre-existing lung disease (moderate to severe chronic obstructive pulmonary disease) or psychiatric disease; chronic kidney disease (eGFR<60).
• Central sleep apnea >10% of respiratory events being central events, rather than obstructive events.

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)
Participants will be randomised to receive either Low intensity inspiratory muscle training or High intensity inspiratory muscle training. An online system (Sealed Envelope) will be used in the process of block randomisation. The unpredictable nature of our method of randomisation promotes allocation concealment to the trial investigators. Therefore, trial investigators will have no influence over which participants end up in which groups.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An online system (Sealed Envelope) will be used in the process of block randomisation. The unpredictable nature of our method of randomisation promotes allocation concealment to the trial investigators. Therefore, trial investigators will have no influence over which participants end up in which groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size was calculated on the basis of our primary objective that inspiratory muscle training will improve blood pressure is OSA patients with cardiovascular risk. Calculations were based on results obtained in a newly published RCT with a similar objective (Ramos-Barrera, DeLucia & Bailey, 2020). The mean difference in blood pressure (systolic and diastolic) between treatment groups pre and post HiIMT and LoIMT treatment (-8.82±4.98 and -2.25±6.85, respectively) were used to calculate the effect size (Cohen's d = 1.1). A sample size of 15 for each treatment group was determined to provide an actual power of 0.8, with alpha 0.05.

To test the treatment effect on primary and secondary outcome measures (high and low intensity inspiratory muscle training) and time point (week 1 vs. week 6) two-way repeated measures mixed model ANOVA will be used. Statistical significance will be set at P<0.05. If ANOVA demonstrates significance, inter and intra - group post hoc analyses will be performed using paired and independent sample t tests, respectively, with an adjusted significance according to the Bonferroni correction.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2021
Actual
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
31/01/2022
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18372 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 32450 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 307522 0
Other
Name [1] 307522 0
Sleep Research Group
Country [1] 307522 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown NSW 2006 Australia
Country
Australia
Secondary sponsor category [1] 308200 0
None
Name [1] 308200 0
None
Address [1] 308200 0
None
Country [1] 308200 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307589 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 307589 0
Ethics committee country [1] 307589 0
Australia
Date submitted for ethics approval [1] 307589 0
10/02/2021
Approval date [1] 307589 0
04/03/2021
Ethics approval number [1] 307589 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107778 0
Prof Peter Cistulli
Address 107778 0
Charles Perkins Centre, Johns Hopkins Dr, Camperdown NSW 2006
Country 107778 0
Australia
Phone 107778 0
+61294632934
Fax 107778 0
Email 107778 0
peter.cistulli@sydney.edu.au
Contact person for public queries
Name 107779 0
Seren Ucak
Address 107779 0
Charles Perkins Centre, Johns Hopkins Dr, Camperdown NSW 2006
Country 107779 0
Australia
Phone 107779 0
+61286270071
Fax 107779 0
Email 107779 0
seren.ucak@sydney.edu.au
Contact person for scientific queries
Name 107780 0
Seren Ucak
Address 107780 0
Charles Perkins Centre, Johns Hopkins Dr, Camperdown NSW 2006
Country 107780 0
Australia
Phone 107780 0
+61286270071
Fax 107780 0
Email 107780 0
seren.ucak@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10191Study protocol    381180-(Uploaded-15-02-2021-13-23-46)-Study-related document.doc
10193Informed consent form    381180-(Uploaded-15-02-2021-13-24-02)-Study-related document.docx
11011Ethical approval    381180-(Uploaded-15-03-2021-13-36-28)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.