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Trial registered on ANZCTR


Registration number
ACTRN12612000536864
Ethics application status
Approved
Date submitted
7/05/2012
Date registered
21/05/2012
Date last updated
17/11/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of non-steroidal anti-inflammatory drugs on hormones and metabolism in overweight men with low testosterone and obstructive sleep apnea (optional partner participation)
Scientific title
Endocrine and metabolic effects of non steroidal anti-inflammatory therapy in overweight, hypogonadal men with obstructive sleep apnea: A pilot study
Secondary ID [1] 280076 0
Nil known
Universal Trial Number (UTN)
u1111-1128-9098
Trial acronym
INFLATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnea 285985 0
Hypogonadism- low testosterone 285986 0
overweight/obesity 285987 0
Condition category
Condition code
Respiratory 286176 286176 0 0
Sleep apnoea
Diet and Nutrition 286771 286771 0 0
Obesity
Metabolic and Endocrine 286778 286778 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
200 mg Celecoxib (oral capsule) once daily for 3 months

Partner: no intervention however completion of questionnaires to gather information related to sleep and breathing as well as general health, sexual health, quality of life, relationships, mood and energy at baseline and at 3 months. This will take 20-30 minutes to complete.
Intervention code [1] 284398 0
Treatment: Drugs
Comparator / control treatment
Placebo control once daily for 3 months (microcellulose capsule)

Partner: observational only- no intervention
Control group
Placebo

Outcomes
Primary outcome [1] 286641 0
Serial repetitive testosterone, estradiol, luteinizing and follicle stimulating hormone concentrations sampled over 12 and 24 hours. Free and total hormone concentrations will be calculated using mass equations and the outcome will be assessed using serum assays.
Timepoint [1] 286641 0
Baseline (10 minute sampling over 12 hours)
3 months (10 minute sampling over 24 hours)
Primary outcome [2] 286642 0
MINMOD (Modified Minimal Model) and HOMA (homeostasis model of assessment) for the measurement of insulin sensitivity
Timepoint [2] 286642 0
Baseline and 3 months
Primary outcome [3] 287078 0
24-hour blood pressure monitoring
Timepoint [3] 287078 0
baseline and 3 months
Secondary outcome [1] 296350 0
Other hormones and binding globulins (eg ACTH, cortisol, testosterone, estradiol, LH, FSH, SHBG)
Timepoint [1] 296350 0
baseline, 1 month, 2 month, 3 month (single blood draws)
Secondary outcome [2] 296351 0
Metabolic markers (insulin, fasting blood glucose, adiponectin, leptin, ghrelin) assessed through serum or plasma assays
Timepoint [2] 296351 0
baseline, 1 month, 2 month, 3 month
Secondary outcome [3] 296352 0
Inflammatory markers (micro-CRP, ESR, WBC, IL-1, IL-6, IL-8, IL-10, IL-1RA and TNF-alpha) assessed through serum or plasma assays
Timepoint [3] 296352 0
baseline, 1 month, 2 month, 3 month
Secondary outcome [4] 296353 0
Cardiovascular health (lipid profiles, anthropometry, body composition (BIA scale), blood pressure, cardiovascular risk as assessed by diagnosis of Metabolic Syndrome and Framingham risk score).
Timepoint [4] 296353 0
baseline, 1 month, 2 month, 3 month
Secondary outcome [5] 296354 0
Polysomnography (PSG)
Timepoint [5] 296354 0
overnight at baseline and 3 months
Secondary outcome [6] 296355 0
General quality of life (QOL) measurements (SF36, ESS, FOSQ, DASS, IWqOL)
Timepoint [6] 296355 0
baseline, 1 month, 2 months and 3 months
Secondary outcome [7] 296356 0
Sex specific quality of life [International Index of Erectile Function (IIEF), Brief Male Sexual Function Inventory (BMSFI)], European Male Ageing Study Sexual Function Questionnaire (EMAS)
Timepoint [7] 296356 0
baseline, 1 month, 2 months, 3 months
Secondary outcome [8] 296360 0
Physical Activity Questionnaire (IPAQ)
Timepoint [8] 296360 0
baseline, 1 month, 2 month, 3 month
Secondary outcome [9] 296361 0
Motivation (compliance, completion) through medication diaries (to ensure participants are taking their medication) and their completion of the trial (attrition rates)
Timepoint [9] 296361 0
baseline, 1 month, 2 month, 3 month
Secondary outcome [10] 296362 0
Sleep quality and activity counts via actigraphy
Timepoint [10] 296362 0
baseline and 3 months
Secondary outcome [11] 296363 0
Partner: Quality of life measurements (SF36, ESS, FOSQ, DASS, MAPQ)
Timepoint [11] 296363 0
baseline and 3 months
Secondary outcome [12] 296364 0
Partner: Relationship quality measurements (SERS, Dyadic Adjustment Scale, Female Sexual Functioning Questionnaire)
Timepoint [12] 296364 0
baseline and 3 months

Eligibility
Key inclusion criteria
1. Males aged 18-65 with obstructive sleep apnea with respiratory disturbance Index (RDI) greater than or equal to 5/hr
2. Overweight or obese (BMI > 27 kg.m-2)
3. Hypogonadism (T < 10 nmol/L) measured on two occasions
4. Waitlisted for CPAP-therapy or treatment refusers
5. Medical history, physical examination and laboratory screening indicating no clinical or laboratory evidence for significant and uncontrolled cardiovascular (ischemic, hypertension), renal, liver disease (serum electrolytes, urea and creatinine, liver function tests and full blood count).
Minimum age
18 Years
Maximum age
65 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Females
2. Anemia
3. Patients currently receiving CPAP-therapy
4. Severe OSA requiring immediate treatment due to severity or increased associated risk (eg Transport worker)
5. Significant and uncontrolled cardiovascular (ischemic heart disease, Congestive heart failure (NYHA II-IV), , hypertension, stroke), renal, liver disease as determined by medical history, physical examination and laboratory screening indicating clinical or laboratory evidence.
6. Doctor diagnosed diabetes.
7. Known hypersensitivity to celecoxib or any of the excipients contained in the celeboxib capsules (lactose, sodium lauryl sulfate, povidine, croscarmellose sodium, magnesium stearate, gelatin, titanium dioxide, iron yellow oxide, indigo carmine).
8. Demonstrated allergic-type reactions to sulfonamides.
9. Patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other non-steroidal anti-inflammatory drugs, including other COX-2 specific inhibitors.
10. Patients using other non-steroidal anti-inflammatory drugs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions (excluding low dose < 150 mg daily aspirin).
11. Active peptic ulceration or gastrointestinal (GI) bleeding.
12. Patients with estimated creatinine clearance <30 mL/min.
13. Severe hepatic impairment (Child-Pugh score 10- classifies the severity of liver disease)
14. Perioperative CABG surgery, unstable (thrombus aetiology), significant IHD, peripheral artery, cerebrovascular disease
15. Drug and alcohol abuse/dependence
16. Shift workers or patients with an irregular sleep / wake routine.
17. Current smokers
18. Current infection
19. Any chronic medical conditions likely, in the judgment of the investigator, that makes the patient unable to complete the study safely, or otherwise unsuitable for the study or that may interfere with or influence study treatment.

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)
The current estimated waitlist for initiation of CPAP treatment is about 2-3 months in the public hospital setting. In this study, patients will be randomised to receive Celecoxib or placebo during this usual waiting period.
Prior to starting this study, a patient will be assessed for eligibility, will have signed an informed consent form and be allocated a unique patient screening number in sequential, ascending chronological order. This number will be a two-digit number prefixed by “S” (e.g. S01, S02 etc) and will be used to identify patients during the screening phase prior to randomisation.
Randomisation will take place on the day of allocation of treatment and involves assigning a unique patient number in sequential, ascending chronological orderaccording to a computer generated randomisation list. To ensure the participant’s anonymity, documents will use the participant’s unique participant identification number (randomisation number).
The investigator and study staff will be blinded to the treatment of any participant. Unblinding of a participant will be possible when required for urgent medical reasons requiring knowledge of treatment for medical care according to the judgment of the principal investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation list prepared by an individual not directly involved in subject assessments. This number will be a two digit number prefixed by “R” (e.g. R01, R02 etc) and will be used to identify the randomised treatment order the patient received.
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
Parallel
Other design features
Option for partner to be enrolled in study to complete questionnaires related to quality of life, relationship and sleep quality. This will provide observational information regarding the effect of changes in testosterone/sleep apnea on the bed partner.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
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)
Recruitment postcode(s) [1] 5081 0
2000
Recruitment postcode(s) [2] 5082 0
2037
Recruitment postcode(s) [3] 5083 0
2050

Funding & Sponsors
Funding source category [1] 284838 0
Government body
Name [1] 284838 0
NHMRC Centre for Integrated Research & Understanding of Sleep
Address [1] 284838 0
Woolcock Institute of Medical Research
University of Sydney NSW 2006
Country [1] 284838 0
Australia
Primary sponsor type
Other
Name
Woolcock
Address
431 Glebe Point Road
Glebe, NSW. 2037. Australia
Country
Australia
Secondary sponsor category [1] 283717 0
Hospital
Name [1] 283717 0
Sydney Local Health District- Ethics Review Committee (RPAH Zone)
Address [1] 283717 0
PO Box M30
Missendon Road, NSW
2050
Country [1] 283717 0
Australia
Other collaborator category [1] 260602 0
Commercial sector/Industry
Name [1] 260602 0
Pfizer Australia
Address [1] 260602 0
38-42 Wharf Road
West Ryde NSW 2114
Country [1] 260602 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286828 0
Sydney Local Health District- Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 286828 0
PO Box M30
Missendon Road
NSW
2050
Ethics committee country [1] 286828 0
Australia
Date submitted for ethics approval [1] 286828 0
25/11/2011
Approval date [1] 286828 0
08/12/2011
Ethics approval number [1] 286828 0
X11-0331
Ethics committee name [2] 286832 0
Sydney South West Area Health Service Human Research Ethics Committee (RPAH Zone)
Ethics committee address [2] 286832 0
PO Box M30
Missenden Road
NSW, 2050
Ethics committee country [2] 286832 0
Australia
Date submitted for ethics approval [2] 286832 0
11/10/2011
Approval date [2] 286832 0
08/12/2011
Ethics approval number [2] 286832 0
X11-0331

Summary
Brief summary
This is a parrallel randomised controlled pilot study designed to investigate the effect of non-steroidal therapy on inflammation in obstructive sleep apnea (OSA) with regard to sleep apnea severity, reproductive function, androgen profile, cardio-metabolic health and quality of life. This study will use the drug celecoxib (Celebrex) which is a marketed drug in Australia that is commonly prescribed for arthritic conditions to relieve joint pain.
Participants will be asked to attend the clinic for a 3 month period involving 5 short visits and 2 overnight stays with PSG and blood sampling.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33867 0
A/Prof Peter Liu
Address 33867 0
Woolcock Institute of Medical Research
431 Glebe Point Road Glebe NSW 2037
Postal Address: PO Box M77 Missenden Road NSW 2050
Country 33867 0
Australia
Phone 33867 0
+61 2 9114 0000
Fax 33867 0
Email 33867 0
camilla.hoyos@sydney.edu.au
Contact person for public queries
Name 17114 0
Miss Liz Machan
Address 17114 0
The Woolcock Institute
431 Glebe Point Road
Glebe
NSW
2037
Country 17114 0
Australia
Phone 17114 0
+61 02 9114 0456
Fax 17114 0
+61 02 9550 5865
Email 17114 0
elizabeth.machan@sydney.edu.au
Contact person for scientific queries
Name 8042 0
Ms Camilla Hoyos
Address 8042 0
The Woolcock Institute
431 Glebe Point Road
Glebe
NSW
2037
Country 8042 0
Australia
Phone 8042 0
+61 02 9114 0409
Fax 8042 0
+61 02 9550 5865
Email 8042 0
camillah@woolcock.org.au

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