The Conversion of ENcapsulated GlucorAphanin, Gut Microbiota Phylogeny and gEnotype Study (ENGAGE) (ENGAGE)
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|ClinicalTrials.gov Identifier: NCT01927666|
Recruitment Status : Completed
First Posted : August 22, 2013
Last Update Posted : September 5, 2016
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The variation in extent of isothiocyanate (ITC) excretion in urine from a capsule delivered dose of glucoraphanin will correlate with differences in (a) the gut microbiota, and (b) the genotype of key polymorphic genes (GSTM1, GSTT1, and other as yet undetermined candidate genes).
Our study is a human dietary intervention in which participants will consume one capsule containing 100mg purified glucoraphanin from broccoli. The levels of glucoraphanin delivered by the capsule are similar to one to two portions of broccoli. As this is purified glucoraphanin there is no myrosinase enzyme present. All conversion of the glucoraphanin, contained within the capsule, to ITC will therefore occur by enzymes found in the gut microbiota.
The ability of the glucoraphanin in the capsule to be metabolised to ITCs by the gut microflora is unknown and will be assessed by measuring ITCs excreted in the urine. The ITCs will be quantified in urine using validated analytical methods.
It has been shown in human dietary intervention studies that the extent of conversion of glucosinolates varies greatly. In order to assess possible causative factors for variation in rate of glucoraphanin metabolism each participant will provide a faecal sample from which their faecal gut microbiota phylogeny will be analysed.
For a small number of participants a second faecal sample will be requested (a maximum of 3 participants). It is our aim to select one low, one medium and one high ITC excreter. Ideally the low and high excreters would be within the lowest and highest 5% excretion of ITC and the third participant would be as close to the mean ITC excretion as possible. The aim would be to culture the faecal microbiota over time with repeat dosing of glucoraphanin in order to select for microbiota that are able to metabolise glucoraphanin. It is known that the main hydrolysis product of glucoraphanin, sulforaphane, has a variety of benefits to human health, however there is no known clinical relevance to being a high, medium or low excreter of ITC.
For each participant a blood sample will also be requested in order that we can assess whether genotype affects the rate of ITC excretion in urine. The GSTM1 genotype and other, as yet, unidentified candidate genes of each participant will be determined. Whether the genotype affects the rate of ITC excretion either alone or in combination with the phylogenetic profile will be assessed.
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Dietary Supplement: 100mg glucoraphanin||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||A Human Intervention Trial Investigating the Conversion of Encapsulated Glucoraphanin to Isothiocyanates; and the Potential Link Between the Extent of the Conversion to an Individual's Gut Microbiota Phylogeny and Genotype.|
|Study Start Date :||December 2012|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||August 2016|
Experimental: dietary intervention
To measure the variation in extent of ITC excretion in urine from a capsule delivered dose of 100mg glucoraphanin
Dietary Supplement: 100mg glucoraphanin
The extent of ITC excretion in urine from a capsule delivered dose of glucoraphanin
- Urinary ITC concentration [ Time Frame: In 24h collections at (i) baseline and (ii) following glucoraphanin capsule administration. ]To measure urinary ITC by HP-LC and LC-MS using validated methods in urine collected during a dietary restriction period both before and after (24 hour urine collection) consumption of a 100mg glucoraphanin capsule.
- Faecal microbiota phylogenetic analysis [ Time Frame: At baseline ]To measure gut microbiota populations by faecal bacteria phylogenetic analysis.
- Genotype [ Time Frame: At baseline ]To determine the genotype of participants for key polymorphic genes by PCR on DNA extracted from blood.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- Men and women aged 18 or over
- Smokers and non-smokers
- Those that live within 40 miles, and 2 hours travelling time, of Norwich
- Women who are or have been pregnant within the last 12 months or breast feeding.
- Those currently suffering from or have ever suffered from any gastrointestinal disease, gastrointestinal disorders and/or surgery including regular diarrhoea and constipation (excluding hiatus hernia unless symptomatic) or study intervention/procedure is contraindicated.
- Have been diagnosed with any long-term medical condition that may affect the study outcome (e.g. diabetes, haemophilia, cardiovascular disease, glaucoma, anaemia). These will be assessed on an individual basis.
- On medication that may affect the study outcome.
- Those that have used antibiotics within the previous one month or on long-term antibiotic therapy.
- Those regularly taking laxatives (once a month or more)
- Those intermittently using pre &/or pro biotics unless willing to abstain for 1 month prior and during study period. (If used regularly (3+ times a week, and for more than one month) and will continue throughout study period then do not exclude).
- Those taking dietary supplements or herbal remedies which may affect the study outcome -unless the participant is willing to discontinue taking them for 1 month prior to starting study. Please note that some supplements may not affect the study and this will be assessed on an individual basis
- Regular/ recent (within 3 months) use of colonic irrigation or other bowel cleansing techniques.
- Parallel participation in another research project which involves dietary intervention and/or sampling of blood
- Any person related to or living with any member of the study team
- Participation in another research project which involves blood sampling within the last four months unless total blood from both studies does not exceed 470mL
- are unwilling to provide GPs contact details
- are unable to provide written informed consent
- are not suitable to take part in this study because of your screening results
- have donated or intend to donate blood within 16 weeks of the first and last study samples
- Those with a body mass index (BMI, kg/m2) <20
- Those who are unable to swallow capsules
- Those who do not have access to a freezer
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01927666
|Institute Of Food Research|
|Norwich, Norfolk, United Kingdom, NR4 7UA|
|Principal Investigator:||Richard Mithen, PhD||Quadram Institute Bioscience|
|Responsible Party:||Quadram Institute Bioscience|
|Other Study ID Numbers:||
|First Posted:||August 22, 2013 Key Record Dates|
|Last Update Posted:||September 5, 2016|
|Last Verified:||November 2015|