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Trial registered on ANZCTR


Registration number
ACTRN12620000338965
Ethics application status
Approved
Date submitted
24/01/2020
Date registered
10/03/2020
Date last updated
10/03/2020
Date data sharing statement initially provided
10/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Testosterone to treat men with mild to moderate Crohn's disease
Scientific title
The effect of Testosterone treatment on disease activity and symptoms in men with mild to moderate Crohn’s disease
Secondary ID [1] 300262 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 315840 0
Hypogonadal 315841 0
Condition category
Condition code
Oral and Gastrointestinal 314124 314124 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a prospective randomised double blind placebo controlled study.
Randomised 1:1, placebo: intervention using random number generator

Group 1: to receive 100mg, once daily, transdermal testosterone cream in addition to existing stable medical therapy for a period of 12 weeks, n=23.
Group 2: matching 100mg, once daily, placebo in addition to existing stable medical therapy for a period of 12 weeks, n=23.

Cream will be applied to the arm with arms being rotated each day to ensure maximum absorbation and less irritation to the skin. All transdermal cream patches will be counted at each visit to ensure compliance with investigational therapy.

Stable therapies include:
a. Immunosuppressant (Azathioprine, 6-Mercaptopurine or methotrexate) for 4 weeks prior to enrollment.
b. 5 ASA medication (mesalazine, olsalazine, sulfasalazine) for 4 weeks prior to enrollment.
c. Corticosteroids for 14 days before enrollment with a dose no higher than the equivalent of 5 mg of prednisolone or 3mg of budesonide.

Patients on biologic medication such as infliximab, vedolizumab, adalimumab or ustekinumab will be excluded.
Intervention code [1] 316540 0
Treatment: Drugs
Comparator / control treatment
transdermal testosterone patch 100mg daily with matching placebo 100mg patch daily.
Treatment is for 12 weeks from date of enrollment into study. Patch's will be worn on participants arms, rotating to the opposite arm each day.

Placebo will include inactive ingredients: cetomacrogol 1000, cetostearyl alcohol, carbopol 940, almond oil, dl-a-tocopheryl acetate (Vitamin E acetate), triethanolamine, Phenonip, butylated hydroxytoluene, anhydrous citric acid, purified water
Control group
Placebo

Outcomes
Primary outcome [1] 322512 0
Composite Outcome. The proportion of intervention and placebo treated participants that achieve clinical remission (CDAI less than 150) AND either a faecal calprotectin level of equal to or less than 100umol/ml and/or simple endoscopic score (SES) of less than 4.

CDAI scores are assessed from patient symptoms and blood tests, Faecal calprotectin is assessed with a faecal sample and simple endoscopic score is assessed using a standard of care colonoscopy.
Timepoint [1] 322512 0
Week 12 post intervention commencement
Secondary outcome [1] 378766 0
The change in IBDQ (Inflammatory bowel disease quality of life) score from baseline (week 0) to end of study (week 12) between the two treatment groups.
Timepoint [1] 378766 0
Week 12 post intervention commencement
Secondary outcome [2] 380491 0
The change in C-reactive protein from baseline (week 0) to end of study (week 12) between the two treatment groups.

Blood samples will be taken and serum assay's anaylsed.
Timepoint [2] 380491 0
Week 12 post intervention commencement
Secondary outcome [3] 380492 0
The change in faecal calprotectin level from baseline (week 0) to end of study (week 12) between the two treatment groups.

Faecal Samples will collected to measure this.
Timepoint [3] 380492 0
Week 12 post intervention commencement
Secondary outcome [4] 380493 0
The change in testosterone levels from baseline (week 0) to end of study (week 12) between the two treatment groups.

Blood samples will be taken and serum assay's anaylsed.
Timepoint [4] 380493 0
Week 12 post intervention commencement
Secondary outcome [5] 380494 0
The change in intestinal ultrasound score (Novak score) from baseline (week 0) to end of study (week 12) between the two treatment groups.
Timepoint [5] 380494 0
Week 12 post intervention commencement

Eligibility
Key inclusion criteria
(i) Adult men (aged 18 years to 70 years) with mild to moderate Crohn’s disease activity as defined by the Crohn’s disease activity index (CDAI) score of 150-300 AND objective evidence of disease activity with either a raised faecal calprotectin equal to or greater than 250 and/or evidence of active inflammation on colonoscopy, with low-normal levels of testosterone (14 nmol/L or less) at screening will be eligible to participate.
(ii) Enter on a stable dose of the following medications at the time of randomisation.
a. Immunosuppressant (Azathioprine, 6MP or methotrexate) for 4 weeks prior to randomisation.
b. 5 ASA medication (mesalazine, olsalazine, sulfasalazine) for 4 weeks prior to randomisation.
c. Corticosteroids for 14 days before randomisation with a dose no higher than the equivalent of 5 mg of prednisolone or 3mg of budesonide.
Minimum age
18 Years
Maximum age
70 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Any patient on biologic (as this defines them as having moderate to severe disease).
(ii) Any patient at imminent risk of a bowel resection.
(iii) Patients having active obstructive symptoms at randomisation.
(iv) A short gut (<1.5m of small bowel remaining) or an ileostomy.
(v) Abnormal liver function test with ALT >3x the upper limit of normal
(vi) An abnormal prostate exam or high PSA levels as defined by laboratory cut-off specific for age.
(vii) A history of prostate or breast cancer.
(viii) Any hypothalamic, pituitary or testicular disease resulting in androgen deficiency necessitating testosterone replacement therapy
(ix) Use of testosterone or other androgens within the past 12 months
(x) Use of high dose opioids, or other medications interfering with testosterone production or action (e.g. long-acting GnRH agonists or androgen receptor antagonists), in the past six months

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)
Patients, treating clinicians and investigators including study nurses will be blinded to treatment allocation. Allocation concealment by the clinical trial pharmacist who will create and administer the randomisation schedule. Investigators will contact the clinical trials pharmacist when a patient has been deemed eligible to be randomised and the pharmcist will then allocate the patient to a treatment group. Un-blinding may be permitted in the event of a participant experiencing a serious adverse event for the purpose of safety reporting and clinical management of the affected patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Prior data indicate that the probability of achieving remission is 0.3. If the true probability of achieving remission for experimental subjects is 0.7, we will need to study 23 experimental subjects and 23 control subjects to be able to reject the null hypothesis that the remission rate for experimental and control subjects are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05. We will use an uncorrected chi-squared statistic to evaluate this null hypothesis.

Recruitment
Recruitment status
Not yet 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)
WA
Recruitment hospital [1] 15675 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [2] 15676 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 29095 0
6000 - Perth
Recruitment postcode(s) [2] 29094 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 304686 0
Charities/Societies/Foundations
Name [1] 304686 0
Spinnaker Health Research Foundation
Address [1] 304686 0
Spinnaker Health Research Foundation
PO Box 480
Fremantle WA 6959
Country [1] 304686 0
Australia
Primary sponsor type
Hospital
Name
Fiona Stanley Hospital
Address
11 Robin Warren Dr
MURDOCH WA 6150
Country
Australia
Secondary sponsor category [1] 305087 0
None
Name [1] 305087 0
Address [1] 305087 0
Country [1] 305087 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305107 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 305107 0
Education Building
Fiona Stanley Hospital
Barry Marshall Parade
Murdoch WA 6150
Ethics committee country [1] 305107 0
Australia
Date submitted for ethics approval [1] 305107 0
26/11/2019
Approval date [1] 305107 0
06/01/2020
Ethics approval number [1] 305107 0
RGS0000003749

Summary
Brief summary
Patients with Crohn’s disease (CD) have bowels that are inflamed, which can make the bowel block off or burst. Many patients end up having surgery. Medications can control CD, but in many patients, it doesn’t work, is expensive, and some get side effects. Studies in animals and humans have shown that if testosterone, the main male sex hormone, is low in the patient’s blood, then signs of inflammation are seen more often. You can increase the testosterone level in the blood by giving testosterone to the patient (e.g. with a skin patch), and higher levels might make the Crohn’s disease better, as shown in some older studies. These older studies had few patients and weren’t very good quality. We want to see if giving testosterone with a skin patch for 12 weeks to men with CD that have low to low-normal levels can make their CD better.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99286 0
Dr Lena Thin
Address 99286 0
Fiona Stanley Hospital
11 Robin Warren Dr
MURDOCH WA 6150
Country 99286 0
Australia
Phone 99286 0
+61 08 6151 1154
Fax 99286 0
Email 99286 0
Lena.Thin@health.wa.gov.au
Contact person for public queries
Name 99287 0
Mr Daniel Lightowler
Address 99287 0
Fiona Stanley Hospital
11 Robin Warren Dr
MURDOCH WA 6150
Country 99287 0
Australia
Phone 99287 0
+61 08 6151 1154
Fax 99287 0
Email 99287 0
Daniel.Lightowler@uwa.edu.au
Contact person for scientific queries
Name 99288 0
Dr Lena Thin
Address 99288 0
Fiona Stanley Hospital
11 Robin Warren Dr
MURDOCH WA 6150
Country 99288 0
Australia
Phone 99288 0
+61 08 6151 1154
Fax 99288 0
Email 99288 0
Lena.Thin@health.wa.gov.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?
Results of patient reported outcomes as well as objective markers of disease such as CRP and CDAI scores will be shared in a de-identified format.
When will data be available (start and end dates)?
Data will be shared at conclusion of data analysis predicated to be in mid to late 2021. No end date to data availibility has been determined.
Available to whom?
Data will be available to fellow researchers in IBD and results will also be shared with Crohn's and Colitis Australia who is the patient advocacy group.
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Data can be obtained through the principle investigator Dr Lena Thin (Lena.Thin@health.wa.gov.au). Data will be shared in a de-identified manner with patient advocacy groups who will disburse in newsletters.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 6597 0
Study protocol
Citation [1] 6597 0
Thin L, Singh A, Venugopal K, Lightowler D, Yeap B. TIC Study Protocol
Link [1] 6597 0
Email [1] 6597 0
Lena.Thin@health.wa.gov.au
Other [1] 6597 0
Summary results
No Results