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Trial registered on ANZCTR


Registration number
ACTRN12612001192875
Ethics application status
Approved
Date submitted
6/11/2012
Date registered
13/11/2012
Date last updated
13/11/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Probiotics to initiate ovulation in women with PolyCystic Ovarian Syndrome (PCOS) and Irritable Bowel Syndrome (IBS)
Scientific title
Prospective non-controlled interventional study investigating the use of oral soluble fibre and probiotic formulation to alter metabolic and reproductive function in women with PolyCystic Ovarian Syndrome (PCOS) and Irritable Bowel Syndrome (IBS)
Secondary ID [1] 281501 0
None
Universal Trial Number (UTN)
Trial acronym
The DOGMA study (Dysbiosis of Gut MicrobiotA)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PolyCystic Ovarian Syndrome (PCOS) 287771 0
Irritable Bowel Syndrome (IBS) 287803 0
Condition category
Condition code
Reproductive Health and Childbirth 288117 288117 0 0
Other reproductive health and childbirth disorders
Alternative and Complementary Medicine 288118 288118 0 0
Other alternative and complementary medicine
Inflammatory and Immune System 288119 288119 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4 weeks oral ingestion of both :
1. soluble fibre in water (5 gm in 200 ml warm water once daily).
2. two probiotic capsules per day (Metagenics Ultra Flora Restore). Each capsule contains 25 billion organisms, including 12.5 Billion Lactobacillus acidophilus NCFM, 12.5 Billion bifidobacterium Lactis Bi-07, 5 Billion lactobacilus rhamnosus and 5 Billion Saccharomyces cerevisiae organisms
Intervention code [1] 286047 0
Treatment: Other
Comparator / control treatment
DOGMA is a prospective study in which patients act as their own control (pre-treatment/ post treatment)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288323 0
To determine if fibre/ probiotic supplementation can reduce inflammation in women with PCOS. The two chosen markers of inflammation are serum C-Reactive Protein (CRP) and Lipopolysaccaride Binding Protein (a marker of immuno-stimulatory endotoxin exposure), assayed by an ELISA.
Timepoint [1] 288323 0
Inflammatory markers will be assessed at study entry and then again 4 weeks later
Secondary outcome [1] 299851 0
1. Reproductive hormones Anti Mullarian Hormone (AMH), Testosterone, sex hormone binding globulin (SHBG).
AMH will be assessed "in house" using an ELISA and testosterone/ SHBG measured by a commercial pathology laboratory.
Timepoint [1] 299851 0
Study entry and then again 4 weeks later (completion of 4 week course fibre/ probiotic)
Secondary outcome [2] 299852 0
2. Blood biochemistry including glucose, insulin, calculated insulin resistance, cholesterol, low and high density lipoproteins (LDL and HDL), homocysteine. These will all be assessed by a commercial pathology laboratory.
Timepoint [2] 299852 0
Study entry and then again 4 weeks later (completion of 4 week course fibre/ probiotic)
Secondary outcome [3] 299853 0
3. Assessment of ovulatory function based on menstrual calender, serum estradiol and progesterone measurements. These will be assessed using a ADVIAR Centaur XP assay platform system (Siemens Healthcare Diagnostics)
Timepoint [3] 299853 0
Entry and day 21 of the study. If ovulation has not been confirmed (serum progesterone > 15 nmol/l) on day 21 sample, a further estrogen and progesterone assessement will be taken on days 28, 35 and 42. If progesterone exceeds 15 nmol/l on either day 28 or 35, nil further blood tests will be taken. The timing of onset of the menstrual period will be followed out to 6 weeks (42 days) after commencement of fibre/ probiotic treatment.
Secondary outcome [4] 299854 0
4. Assessment of gastrointestinal function. This will be done using the Rome III criteria for the diagnosis of Irritable Bowel Syndrome (IBS) and the Birmingham IBS symptom severity questionnaire.
Timepoint [4] 299854 0
Screening examination before initiation of investigational treatment (fibre/ probiotic) and 28 days later.
Secondary outcome [5] 299855 0
5. Anthropometric assessment. Body mass Index (height/ weight), percentage body fat by bioelectrical impedance analyzer, waist circumference
Timepoint [5] 299855 0
Study entry and day 28 of study
Secondary outcome [6] 299857 0
6. Diet assessment by 3 day food frequency assessment
Timepoint [6] 299857 0
study recruitment and day 28 0f the study

Eligibility
Key inclusion criteria
1. Presence of PolyCystic Ovarian Syndrome based on the Rotterdam Criteria
2. Presence of Irritable Bowel Syndrome based on the Rome III criteria
3. waist circumference > 88 cm (marker of insulin resistance)
Minimum age
20 Years
Maximum age
39 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Non functional bowel disorder (e.g. inflammatory bowel disease, diverticulitis, colon cancer).
2. Autoimmune disease (e.g. SLE, rheumatoid arthritis)
3. active infection
4. hormonal contraception
5. medication that may effect the bowel flora (e.g. antibiotics, laxatives).
6. immuno-supressive medication (excluding topical or inhaled corticosteroids).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants with PCOS and IBS will be invited by newspaper and online advertisements to be screened for their involvement in the trial. Provided they meet the inclusion/ exclusion criteria they will all then be allocated to 4 weeks (28 days) of fibre and probiotic supplementation. No placebo will be used and therefore allocation concealment is not required.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not relevant
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 286315 0
University
Name [1] 286315 0
University South Australia
Address [1] 286315 0
North Terrace, Adelaide, South Australia, 5000
Country [1] 286315 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
North Terrace, Adelaide, South Australia, 5000
Country
Australia
Secondary sponsor category [1] 285075 0
Commercial sector/Industry
Name [1] 285075 0
Health World Limited
Address [1] 285075 0
741 Nudgee Rd, Northgate, Queensland, 4013
Country [1] 285075 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288352 0
University of South Australia Human Ethics Committee
Ethics committee address [1] 288352 0
North Terrace, Adelaide, South Australia, 5000
Ethics committee country [1] 288352 0
Australia
Date submitted for ethics approval [1] 288352 0
Approval date [1] 288352 0
01/11/2012
Ethics approval number [1] 288352 0
29368

Summary
Brief summary
Polycystic ovary syndrome (PCOS) is the most common cause for women experiencing menstrual irregularity and anovulation (not releasing an egg each month), affecting up to 10% of the population. While the cause for PCOS is not fully understood, certain probable links have been identified. Almost half the individuals with PCOS have an excess of adipose (fat) tissue stored around their waist, impaired sugar metabolism (insulin resistance) and high levels of fats / cholesterol in their blood stream (dyslipidemia). The excess fat tissue is believed to activate the bodies immune system, causing inflammation which then stops ovulation and increases the ovaries production of testosterone. It is this raised testosterone that may cause acne and excess body hair- a common feature of PCOS.
Being over weight and a diet high in saturated fat have both been independently linked with inflammation. Furthermore, women with PCOS are known to have signs of increased inflammation in their body compared to healthy women without PCOS. Work by our group has shown that individuals with PCOS have less than ideal diets, with high intakes of saturated fat, and a higher body mass index (BMI) than aged matched fertile counterparts. Other groups have also shown that PCOS patients have a high saturated fat intake. We have previously proposed that a high fat / low fibre diet will create disturbances in bowel bacteria, with an overgrowth of “bad” bacteria which can then pass across the gut wall into the blood stream and activate the woman’s immune system. The resulting inflammation is known to produce insulin resistance with resulting high blood levels of insulin interfering with normal egg development and ovulation, while driving up the ovaries production of testosterone, potentially causing acne and excess body hair.
Probiotics are “good” or beneficial bacteria that are present in food sources such as yogurt, fermented milk drinks or can be taken as powder and capsule supplements. Probiotics are useful treatments for gastro-intestinal conditions such as constipation, antibiotic associated diarrhoea and irritable bowel syndrome (IBS). All of these clinical conditions are linked with an increase in “bad” bacteria in the gut and have been shown to cause inflammation in the gut and in the rest of the body. Probiotic “good” bacteria have the ability reduce the number of “bad” bacteria in the gut, while also helping stop these “bad” bacteria passing through the gut wall into the blood stream where they can activate inflammation. Therefore, we propose that by giving probiotic “good” bacteria supplements to women with PCOS and symptoms of excess “bad” bacteria in their gut (bloating, pain, constipation or diarrhoea) we may be able to reduce inflammation in the body, thereby reducing insulin and testosterone levels and re-starting ovulation. This is the primary research question of this study.
Trial website
None
Trial related presentations / publications
Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA)--a novel theory for
the development of Polycystic Ovarian Syndrome. Med Hypotheses. 2012
Jul;79(1):104-12.
Public notes

Contacts
Principal investigator
Name 34922 0
Address 34922 0
Country 34922 0
Phone 34922 0
Fax 34922 0
Email 34922 0
Contact person for public queries
Name 18169 0
A/Professor Kelton Tremellen
Address 18169 0
180 Fullarton Road
Dulwich
South Australia, 5065
Country 18169 0
Australia
Phone 18169 0
61 8 83338113
Fax 18169 0
61 8 83338188
Email 18169 0
ktremellen@repromed.com.au
Contact person for scientific queries
Name 9097 0
A/Professor Kelton Tremellen
Address 9097 0
180 Fullarton Road
Dulwich
South Australia, 5065
Country 9097 0
Australia
Phone 9097 0
61 8 83338113
Fax 9097 0
Email 9097 0
ktremellen@repromed.com.au

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