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Trial registered on ANZCTR


Registration number
ACTRN12611000887976
Ethics application status
Approved
Date submitted
18/08/2011
Date registered
19/08/2011
Date last updated
25/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of cranberry capsules on cystitis in men treated with radiation for prostate cancer
Scientific title
The efficacy of cranberry capsules in the prevention and management of acute radiation cystitis in men treated with radiation for prostate cancer
Secondary ID [1] 262871 0
Nil
Universal Trial Number (UTN)
U1111-1123-8135
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute non-infectious radiation cystitis 270586 0
Prostate Cancer 270600 0
Condition category
Condition code
Renal and Urogenital 270758 270758 0 0
Other renal and urogenital disorders
Cancer 270765 270765 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who have given written informed consent will be randomized to to either the cranberry arm or the placebo arm by the PI, Dr Patries Herst. Each participant will be given a numbered brown glass bottle (patient 01 will have bottle 01 etc.) containing either 70 cranberry or 70 placebo capsules at the start of their RT treatment.

The participants will take one capsule a day during breakfast from the first day of treatment and continue until all the capsules have been taken (10 weeks).

Durning the trial, participants are not allowed to take foods, drinks or supplements containing cranberries, blueberries or blackberries and limit consumption of grapes and wine.

The cranberry capsules contain 72mg proanthocyanidins (PACs) each.
Intervention code [1] 269219 0
Treatment: Other
Intervention code [2] 269220 0
Prevention
Comparator / control treatment
The placebo control capsules. contain colloidal silica, magnesium stearate, cellulose and gelatin. All capsules will be opaque, making them indistinguishable from the cranberry capsules. Participants randomized to the control arm will follow exactly the same regimen as the patients randomized to the treatment arm but tale placebo capsules instead of cranberry capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 279453 0
To determine if cranberry capsules reduce the severity of cystitis.
This will be assessed using a slightly modified urinary domain of the Expanded Prostate Index Composite (EPIC) measure (Wei et al.Urology, 2000. 56(6): p. 899-905). This is a 2 page questionnaire that aks the men about different urinary symptoms and how much bother each of these are in their daily life using simple Likert scales. Symptoms include: pain/burning, blood in urine, use of ural and urinary control.
Timepoint [1] 279453 0
The first assessment will be done before radiation therapy begins, then once a week for 10 weeks until there are no more capsules left.
Secondary outcome [1] 287677 0
To determine if cranberry capsules decrease the incidence of cystitis.This will be assessed using a slightly modified urinary domain of the Expanded Prostate Index Composite (EPIC) measure (Wei et al.Urology, 2000. 56(6): p. 899-905). This is a 2 page questionnaire that aks the men about different urinary symptoms and how much bother each of these are in their daily life using simple Likert scales. Symptoms include: pain/burning, blood in urine, use of ural and urinary control.
Timepoint [1] 287677 0
End of the trial when all the capsules have been used up.
Secondary outcome [2] 287678 0
To determine if cranberry capsules increase the time and dose to onset of cystitis
Timepoint [2] 287678 0
Time and dose to onset of cystitis
Secondary outcome [3] 287679 0
To determine if cranberry capsules decrease the need for symptom relief (ural).
Timepoint [3] 287679 0
This will be evaluated weekly with the modified EPIC scale. One question on the scale specifically asks how often the men have used ural in the previous week.

Eligibility
Key inclusion criteria
All men receiving radiation therapy for prostate cancer at the Department of Radiation Therapy in Dunedin Hospital.
Minimum age
No limit
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Men who have had previous RT to the pelvis, have systemic disease, anallergy to cranberries or a history of kidney stones are excluded from this trial.

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)
Randomization will be carried out by the PI, Dr Patries Herst, who is a senior lecturer at the University of Otago in Wellington, has no patient contact and is not involved in any aspects of the day to day running of the trial.

Bottles containing cranberry capsules and bottles containing placebo capsules will be allocated a number between 1 and 40 by the PI using computer-generated random numbers (provided by the biostatistician). Patients, clinicians and research assistants will be blinded with respect to the content of the capsules. Unblinding will occur after all data have been collected at the end of the trial, followed by an in depth data analysis by the PI.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random numbers provided by the University's biostatistician.
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
One group of patients will receive cranberry capsules, one will receive placebo capsules
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
EPIC scores were analysed with SAS v9.3 (SAS Institute Inc., Cary, NC). The mean and maximum scores were compared with non-parametric Wilcoxon rank-sum tests and analysis of variance on the ranked data [25] with adjustment for whether or not the symptom was present at baseline. Analysis of variance on the rank data with terms for study group and either whether the patient had baseline symptoms or whether they had the high or low hydration regimen, and their interactions, were used to assess the statistical significance of any differences between sub-groups. A p-value <0.05 was treated as being statistically significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2011
Actual
7/08/2012
Date of last participant enrolment
Anticipated
11/02/2013
Actual
20/03/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
41
Recruitment outside Australia
Country [1] 3797 0
New Zealand
State/province [1] 3797 0

Funding & Sponsors
Funding source category [1] 269689 0
University
Name [1] 269689 0
University of Otago
Country [1] 269689 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Creative Energy LTD
Address
Natural Health
Wingate Industrial Park
80-82 Eastern Hutt Road
Taita, Lower Hutt
Wellington 5019.
Country
New Zealand
Secondary sponsor category [1] 268725 0
Hospital
Name [1] 268725 0
Dunedin Public Hospital
Address [1] 268725 0
Southern Blood and Cancer Centre
Private bag 1921
Dunedin 9054
Country [1] 268725 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271650 0
Upper South A Regional Ethics Committee
Ethics committee address [1] 271650 0
Ministry of Health
Level 4, Charles Luney Building
250 Oxford Terrace
Christchurch 8011
Ethics committee country [1] 271650 0
New Zealand
Date submitted for ethics approval [1] 271650 0
02/08/2011
Approval date [1] 271650 0
15/08/2011
Ethics approval number [1] 271650 0
URA/11/08/038

Summary
Brief summary
The overarching aim of the proposed trial is to investigate whether or not cranberry capsules are superior to placebo control capsules in reducing the severity and incidence of acute radiation cystitis occurring in men with prostate cancer.

Background
Prostate cancer is the most common cancer among older men in developed countries. Cancer Statistics NZ reported that in 2008, 2798 non-Maori men were diagnosed with prostate cancer and 635 men (23%) died of this disease in that year. During that same year, 141 Maori men were diagnosed and 35 men (25%) died of the disease [1]. Treatment for prostate cancer can include surgery, radiation therapy and hormone therapy, depending on the stage, location, co-morbidities and patient preferences. Acute radiation-induced cystitis is a common side effect of radiation therapy to the pelvis, with up to 40% of men suffering from cystitis to some extent [2, 3]. Acute symptoms occur within weeks of radiation treatment and include urinary urgency, frequency, dysuria, and hematuria. Currently there is no effective treatment for radiation cystitis. Standard care for radiation cystitis in the Southern Blood and Cancer Service in Dunedin Hospital radiation cystitis is ural, a urinary alkalinizer which relieves symptoms but does not affect cystitis.

Because radiation cystitis is caused by free radical damage to the bladder lining [4], therapies that decrease the number of free radicals in the bladder may decrease its severity [5]. Proanthocyanidins (PACs), phytochemicals found in the North American cranberry, have dose dependent radical scavenging, anti-bacterial and anti-carcinogenic properties [6-11]. A recent Cochrane Review reported that cranberry juice reduces the incidence of recurrent infectious cystitis (urinary tract infections) in young women by inhibiting adhesion of pathogenic E.coli bacteria to the bladder wall [12, 13].

The effect of cranberries on radiation cystitis has so far not been investigated. This double blinded placebo controlled pilot study will investigate the effect of cranberry capsules on the severity and incidence of acute radiation cystitis in men with prostate cancer. A shortened modified version of the Expanded Prostate Index Composite (EPIC) measure [14] will be used to assess the extent of cystitis

References
1. MOH, Cancer Statistics New Zealand. New Zealand Ministry of Health, 2010.
2. McCammon et al. Int. J. Radiat. Oncol. Biol. Phys., 2009. 75(2): p. 413-420.
3. Pervez et al. Int. J. Radiat. Oncol. Biol. Phys., 2010. 76(1): p. 57-64.
4. Suresh et al. J. Clin. Pathol., 1993. 46(3): p. 228-231.
5. Greenberger, and Epperly. In Vivo, 2007. 21(2): p. 141-146.
6. Côté et al. Crit. Rev. Food. Sci. Nutr. , 2010. 50(7): p. 666-679.
7. Déziel et al. J. Cell. Biochem. , 2010. 111(3): p. 742-754.
8. Menghini et al. J. Biol. Regul. Homeost. Agents, 2011. 25(1): p. 27-35.
9. Pappas and Schaich. Critical Reviews in Food Science and Nutrition, 2009. 49: p. 741-781.
10. Seeram. J. Agric. Food Chem., 2008. 56: p. 627-629.
11. Seeram et al. J. Agric. Food Chem., 2004. 52: p. 2512-2517.
12. Jepson and Craig. Cochrane Database Syst. Rev., 2008. 23(1): p. CD001321.
13. Howell et al. BMC Infectious Diseases, 2010. 10: p. 94-105.
14. Wei et al. Urology, 2000. 56(6): p. 899-905.
Trial website
Trial related presentations / publications
Hamilton, K.A., Bennett, N.C., Purdie, G.L., Herst, P.M. Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded placebo controlled pilot study. Supportive Care in Cancer, Support Care Cancer. 2015 Jan;23(1):95-102. doi: 10.1007/s00520-014-2335-8. Epub 2014 Jul 4.
Public notes
Attachments [1] 649 649 0 0
/AnzctrAttachments/343363-Hamilton, 2014.pdf

Contacts
Principal investigator
Name 33041 0
Dr Patries Herst
Address 33041 0
Senior Lecturer Department of Radiation Therapy University of Otago, Wellington POBox 7343 Wellington South 6242 Wellington
Country 33041 0
New Zealand
Phone 33041 0
+64-4-3855475
Fax 33041 0
+64-4-3855375
Email 33041 0
[email protected]
Contact person for public queries
Name 16288 0
Dr Patries Herst
Address 16288 0
Senior Lecturer
Department of Radiation Therapy
University of Otago, Wellington
POBox 7343
Wellington South 6242
Wellington
Country 16288 0
New Zealand
Phone 16288 0
+64-4-3855475
Fax 16288 0
+64-4-3855375
Email 16288 0
[email protected]
Contact person for scientific queries
Name 7216 0
Dr Patries Herst
Address 7216 0
Senior Lecturer
Department of Radiation Therapy
University of Otago, Wellington
POBox 7343
Wellington South 6242
Wellington
Country 7216 0
New Zealand
Phone 7216 0
+64-4-3855475
Fax 7216 0
+64-4-3855375
Email 7216 0
[email protected]

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