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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]

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)

Irritable Bowel Syndrome (IBS)

Condition category

Condition code

Reproductive Health and Childbirth

Other reproductive health and childbirth disorders

Alternative and Complementary Medicine

Other alternative and complementary medicine

Inflammatory and Immune System

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]

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]

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]

Inflammatory markers will be assessed at study entry and then again 4 weeks later

Secondary outcome [1]

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]

Study entry and then again 4 weeks later (completion of 4 week course fibre/ probiotic)

Secondary outcome [2]

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]

Study entry and then again 4 weeks later (completion of 4 week course fibre/ probiotic)

Secondary outcome [3]

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]

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]

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]

Screening examination before initiation of investigational treatment (fibre/ probiotic) and 28 days later.

Secondary outcome [5]

5. Anthropometric assessment. Body mass Index (height/ weight), percentage body fat by bioelectrical impedance analyzer, waist circumference

Timepoint [5]

Study entry and day 28 of study

Secondary outcome [6]

6. Diet assessment by 3 day food frequency assessment

Timepoint [6]

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

Sex

Females

Can healthy volunteers participate?

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

1/12/2012

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]

University

Name [1]

University South Australia

Address [1]

North Terrace, Adelaide, South Australia, 5000

Country [1]

Australia

Primary sponsor type

University

Name

University of South Australia

Address

North Terrace, Adelaide, South Australia, 5000

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Health World Limited

Address [1]

741 Nudgee Rd, Northgate, Queensland, 4013

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of South Australia Human Ethics Committee

Ethics committee address [1]

North Terrace, Adelaide, South Australia, 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

01/11/2012

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

A/Professor Kelton Tremellen

Address

180 Fullarton Road
Dulwich
South Australia, 5065

Country

Australia

Phone

61 8 83338113

Fax

61 8 83338188

[email protected]

Contact person for scientific queries

Name

A/Professor Kelton Tremellen

Address

180 Fullarton Road
Dulwich
South Australia, 5065

Country

Australia

Phone

61 8 83338113

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically