Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000158864
Ethics application status
Approved
Date submitted
20/01/2021
Date registered
16/02/2021
Date last updated
8/06/2022
Date data sharing statement initially provided
16/02/2021
Date results information initially provided
15/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of combination drug therapy to treat sleep apnoea
Scientific title
The effect of antihistaminergic and antimuscarinic drugs on disease severity in adults with obstructive sleep apnoea
Secondary ID [1] 303168 0
n/a
Universal Trial Number (UTN)
Trial acronym
Beta-OxyOSA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 320287 0
Condition category
Condition code
Respiratory 318213 318213 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised, placebo-controlled, two arm crossover study (~1 week washout between visits): Arm 1: oral capsules of betahistine (96 mg) and oxybutynin (5mg) immediately prior to sleep (single night, in laboratory study)
Arm 2: placebo oral capsules immediately prior to sleep (single night, in-laboratory study)
Interventions will be administered by a study investigator on each laboratory visit just prior to sleep for these acute sleep studies to ensure adherence.
Intervention code [1] 319469 0
Treatment: Drugs
Comparator / control treatment
Placebo (maize starch capsules) compared to visually identical capsules of active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 326199 0
Sleep apnoea severity using the apnoea/hypopnoea index (AHI) assessed from overnight polysomnogram
Timepoint [1] 326199 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [1] 390479 0
Sleep efficiency from overnight polysomnogram
Timepoint [1] 390479 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [2] 390480 0
Oxygen desaturation index from overnight polysomnogram measured using pulse oximetry
Timepoint [2] 390480 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [3] 390481 0
Arousal index and other standard polysomnography parameters measured from overnight polysomnogram
Timepoint [3] 390481 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [4] 390482 0
Daytime sleepiness measured by Karolinska Sleepiness Scale questionnaire
Timepoint [4] 390482 0
Questionnaire administered upon waking after overnight sleep study after placebo and drug nights.
Secondary outcome [5] 390483 0
Polysomnography-derived endotype (pharyngeal muscle responsiveness)
Timepoint [5] 390483 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [6] 390484 0
Next day alertness (breaking reaction time) measured by driving simulator performance
Timepoint [6] 390484 0
After each single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [7] 391855 0
Next day alertness (steering deviation) measured by driving simulator performance
Timepoint [7] 391855 0
After each single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [8] 391856 0
Polysomngraphy-derived endotype (loop gain)
Timepoint [8] 391856 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [9] 391857 0
Polysomnography-derived endotype ( upper airway collapsibility)
Timepoint [9] 391857 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)
Secondary outcome [10] 391858 0
Polysomnography-derived endotype (arousal threshold)
Timepoint [10] 391858 0
Single overnight acute sleep studies (placebo and drug nights, approximately 1 week washout between studies)

Eligibility
Key inclusion criteria
Otherwise healthy adults with obstructive sleep apnoea aged 18 - 75 years with BMI < 40.0kg/m^2 at screening.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Any acute or chronic medical condition other than well controlled hypertension , hyperlipidemia, compensated diabetes.
• Any medication known to influence breathing, sleep/arousal or muscle physiology.
• Any medication known to interact with mono amino oxidases.
• Inability to sleep supine (data collection requires a majority of supine position and body position is controlled)
• Any other condition which in the opinion of the investigator would present an unreasonable risk to the participant, or which would interfere with their participation in the study or unduly confound study interpretation, or would render the participant unable or unlikely to understand or comply with the study design, or the receive the specified medications.
• Allergy to oxymetazoline HCl, betahistine dihydrochloride, oxybutynin hydrochloride.
• Bronchial asthma and atopic family history, which are more susceptible to associate with bronchospasm following betahistine dihydrochloride administration.
• Gastric or peptic ulcer, which might be worsened by betahistine dihydrochloride administration on an empty stomach.
• Benign prostatic hyperplasia or urinary retention, which can be exacerbated by the antimuscarinic agent.
• Individuals with underlying cardiac disease, such as arrhythmias.
• Individuals with previous or recent history of phaeochromocytoma.
• Individuals taking tricyclic antidepressants.
• History of moderate or severe renal impairment.
• Pregnancy or breast feeding.

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 via randomised code generated by the independent pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A blocked sequence (groups of four) will be generated independently by the study pharmacist prior to the beginning of the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome of a difference in AHI between the placebo and drug conditions for each participant will be assessed using two-tailed paired t-test or Wilcoxon signed rank test as appropriate according to normality distribution.


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/02/2021
Actual
18/02/2021
Date of last participant enrolment
Anticipated
30/11/2022
Actual
3/06/2021
Date of last data collection
Anticipated
31/12/2022
Actual
11/06/2021
Sample size
Target
12
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 32523 0
5042 - Flinders University

Funding & Sponsors
Funding source category [1] 307575 0
University
Name [1] 307575 0
Flinders University
Country [1] 307575 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Road, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 308267 0
None
Name [1] 308267 0
Address [1] 308267 0
Country [1] 308267 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307634 0
Southern Adelaide Clinical HREC
Ethics committee address [1] 307634 0
Flinders Medical Centre,
Southern Adelaide Local Health Network, SA Health
Flinders Drive, Bedford Park SA 5042
Ethics committee country [1] 307634 0
Australia
Date submitted for ethics approval [1] 307634 0
01/10/2020
Approval date [1] 307634 0
18/12/2020
Ethics approval number [1] 307634 0
248.20

Summary
Brief summary
Aim:
To determine in a proof-of-concept study if re-purposing existing approved medications that target the sleep/wake system and upper airway muscle control reduce sleep apnoea severity.
Research design: randomised, double -blind, placebo-controlled, cross-over.
Methods: Participants will be required to attend 2 overnight visits, each separated by 1 week in the sleep laboratory. Standard sleep monitoring equipment will be applied including: electrodes on the surface of the head, face and chest to monitor wakefulness and sleep, a sensor placed on the finger to monitor oxygen levels, bands placed around the chest and abdomen along with airflow sensors or a mask over the nose to monitor breathing.
Participants will be randomised to receive either a placebo (sugar pill) or a combination of two medications (betahistine 96 mg + oxybutynin 5 mg) just prior to sleep.
Trial website
n/a
Trial related presentations / publications
n/a
Public notes
n/a

Contacts
Principal investigator
Name 107942 0
Prof Danny Eckert
Address 107942 0
Adelaide Institute for Sleep Health
Flinders University
Level 2, Mark Oliphant Building,
5 Laffer Drive
Bedford Park SA 5042
Country 107942 0
Australia
Phone 107942 0
+61 874219780
Fax 107942 0
Email 107942 0
danny.eckert@flinders.edu.au
Contact person for public queries
Name 107943 0
Carolin Tran
Address 107943 0
Adelaide Institute for Sleep Health
Flinders University
Level 2, Mark Oliphant Building,
5 Laffer Drive
Bedford Park SA 5042
Country 107943 0
Australia
Phone 107943 0
+61 874219873
Fax 107943 0
Email 107943 0
aish.sleeplab@flinders.edu.au
Contact person for scientific queries
Name 107944 0
Danny Eckert
Address 107944 0
Adelaide Institute for Sleep Health
Flinders University
Level 2, Mark Oliphant Building,
5 Laffer Drive
Bedford Park SA 5042
Country 107944 0
Australia
Phone 107944 0
+61 874219780
Fax 107944 0
Email 107944 0
danny.eckert@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual data will be provided for key outcomes in the primary publication of the study
When will data be available (start and end dates)?
After the study is complete and the findings are published. No end date.
Available to whom?
Via journal publication to any interested readers
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Via journal publication


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
No additional documents have been identified.