Intestinal DiseasesCHS-UKNCT02772861
Citrulline Challenge Study for Healthy Subjects in the United Kingdom
A study testing Amino Acid Supplement - One dose and 3-Methylhistidine in people with Intestinal Diseases, run by University College, London at 1 site in United Kingdom.
Trial summary
There are many forms of small bowel disease but their direct consequences on small bowel function are often very hard, if not impossible, to establish. It would be helpful if there was a reliable blood test to find out how well cells in the intestine are working. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Intestinal Diseases
- What is being tested?
- Amino Acid Supplement - One dose and 3-Methylhistidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2011to May 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers fasted for at least 12 hours
- Males and females aged at least 18
Who cannot join
- Consumption of coffee or alcohol within 12 hours
- Pregnancy
- Use of any regular medication
- Any significant past medical history
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised Cross-over Single-site Study on the Bioavailability of Citrulline After an Oral Bolus of Citrulline, Glutamine, Arginine, 3-Methylhistidine or Placebo in Healthy Subjects
There are many forms of small bowel disease but their direct consequences on small bowel function are often very hard, if not impossible, to establish. It would be helpful if there was a reliable blood test to find out how well cells in the intestine are working. The amino acid citrulline is produced mainly by these cells, and therefore holds promise as a biological marker. Some previous studies have shown that fasting citrulline gave a good indication as to how many intestinal cells were present. However, other authors have not been able to confirm this.
Most of the citrulline in the blood is derived from another amino acid, glutamine, in a metabolic process that occurs in the intestinal cells, and most of the remainder comes from another amino acid, arginine. A further potential marker of intestinal cell function is the amino acid 3-methylhistidine. It is possible that a dynamic test, which incorporates time for conversion from one amino acid to another in the intestinal cells, might perform better.
Read more
The investigators therefore propose a study of oral glutamine, arginine, and 3-methylhistidine compared with citrulline itself or placebo (glucose) as it is hypothesized that these might increase the amount of citrulline more reproducibly. An initial study in healthy subjects is required to establish whether this is true, and if so to provide a normal range prior to investigation of patients who have or who might have the short bowel syndrome, and in whom the test would be clinically useful.
In this study, the subjects will take each of the amino acids and placebo in random order. Between each 6 hour-long visit the subjects will have at least one week where they are independent of the research team and during which they can behave normally. During each visit subjects will have a sequence of blood samples from an in-dwelling venous cannula, taken before and over 6 hours after a single small oral dose of that day's amino acid given as a small volume drink. Urine will also be collected for amino acid assay.
Read the detailed description
Purpose and Design The purpose of the study is to determine the value of measuring citrulline after oral challenge, aiming to examine this as a function of enterocyte mass in patients with short bowel syndrome. The investigators hope to accumulate sufficient preliminary data in order to develop a new biochemical test for assessing absorption in future patient groups.
All subjects will provide written informed consent prior to their inclusion in the study. The study will be performed in accordance with International Conference on Harmonisation Guidelines for Good Clinical Practice (ICH GCP), the Helsinki Declaration and national regulations. Information about the study will be provided during one-on-one interviews with the help of a summary brochure which will be given to all potential subjects.
The study has been considered by the UK Medicines Agency, Medicines and Healthcare products Regulatory Agency (MHRA), and they agree that it is not a clinical trial of an investigational medicinal product.
Recruitment
- Potential participants will be identified by the investigator's team. The sources will include hospital and investigator databases.
- If permitted, advertisements will be posted for this study on University College London (UCL) electronic news sites, disseminated via UCL staff and student emails, with fliers to be posted on physical notice boards at UCL. Direct invitations from the researchers may also be attempted.
- Healthy volunteers will be offered £7.85/hour for their participation in this study.
Consent Written informed consent will be obtained before any study-specific procedures are carried out.
All participants will be free to withdraw from the study at any time.
Risk, burdens and benefits Apart from the small risks associated with venous access the study is expected to be without important hazard. The agents to be administered are essentially constituents of the normal diet.
There is no expectation that participants will benefit from being in this study.
Confidentiality All data provided to the sponsor or designee will be identified only by subject number or initials, thereby ensuring that the subject's identity remains unknown.
What will happen at the end of the study? Participants will be given a summary of the key results and the opportunity for further discussion on request.
- Conditions
- Intestinal Diseases
- Being tested
- Amino Acid Supplement - One dose, 3-Methylhistidine
- Medical subject headings
- Intestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amino Acid Supplement - One doseDietary supplement
20gr
3-MethylhistidineDietary supplement
120mgr
| Study group | Role | What they receive |
|---|---|---|
| Citrulline | Experimental | Citrulline is a non-protein amino acid that is present in substantial amounts in watermelon (Citrullus vulgaris), with a mean content of 2.1 mg/g fresh weight, ranging from 0.5 to 3.6 mg/g according to variety. The oral dose can reach 20 g, which was administered orally in the present study in one single dose, followed by a washout period of one week Amino Acid Supplement - One dose Receives: Dietary Supplement: Amino Acid Supplement - One dose |
| Glutamine | Experimental | L-glutamine is a protein amino acid found in proteins of all life forms. It is classified as a semi-essential or conditionally essential amino acid. This means that under normal circumstances the body can synthesize sufficient l-glutamine to meet physiological demands. However, there are conditions where the body cannot do so. Recently, l-glutamine has come to be regarded as one of the most important of the amino acids when the body is subjected to such metabolic stress situations as trauma (including surgical trauma), cancer, sepsis and burns. In the present study, glutamine was administered orally in one single dose of 20 g, followed by a washout period of one week.
Amino Acid Supplement - One dose Receives: Dietary Supplement: Amino Acid Supplement - One dose |
| Arginine | Experimental | Arginine was administered orally in 20 g for one single dose, followed by a washout period of 1 week.
Amino Acid Supplement - One dose Receives: Dietary Supplement: Amino Acid Supplement - One dose |
| 3-Methyl-Histidine | Experimental | This amino acid is made by methylation of the actin and myosin peptide chains in the muscle. Metabolism after intravenous administration of L-3-methylhistidine involves excretion in the urine of 75% of the administered dose in 24 h and 95% in 48 h.
3-Methyl-Histidine was administered orally in 120 mg for one single dose, followed by a washout period of 1 week. Receives: Dietary Supplement: 3-Methylhistidine |
| Placebo | Placebo comparator | Dextrose (glucose) was used in a dose of 20 g in this study. Receives: Dietary Supplement: Amino Acid Supplement - One dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC) for citrulline
The primary end point for this study will be the Area Under the Curve (AUC) for citrulline after each oral load. This is the fraction of the administered dose that reaches the systemic circulation. Bioavailability is 100% for intravenous injection. It varies for other routes depending on incomplete absorption, first pass hepatic metabolism etc. Thus one plots plasma concentration against time, and the bioavailability is the AUC. The analysis of this continuous pharmacokinetic parameter will be performed on the plasma concentration-time data, using Statistical Package for the Social Sciences (SPSS) 17.0, Stata 10.0, Statistical Analysis System (SAS) and Sigma Plot.
Measured: predose, 15,30,45,60,90,120,180,360 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2016 (estimated)
- Study startAug 2011
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intestinal DiseasesStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alastair Forbes, MD, FRCP, Principal investigator, University College London, Centre for Gastroenterology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02772861
- Sponsor's protocol ID
- 10/0458
- Acronym
- CHS-UK
- Status last verified
- May 2016
- First submitted
- 5 Dec 2011
- Last updated
- 16 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Cross-over Single-site Study on the Bioavailability of Citrulline After an Oral Bolus of Citrulline, Glutamine, Arginine, 3-Methylhistidine or Placebo in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02772861
- Acronym / sponsor ID
- CHS-UK / 10/0458
- Conditions
- Intestinal Diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 16 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are many forms of small bowel disease but their direct consequences on small bowel function are often very hard, if not impossible, to establish. It would be helpful if there was a reliable blood test to find out how well cells in the intestine are working. The amino acid citrulline is produced mainly by these cells, and therefore holds promise as a biological marker. Some previous studies have shown that fasting citrulline gave a good indication as to how many intestinal cells were present. However, other authors have not been able to confirm this.
Most of the citrulline in the blood is derived from another amino acid, glutamine, in a metabolic process that occurs in the intestinal cells, and most of the remainder comes from another amino acid, arginine. A further potential marker of intestinal cell function is the amino acid 3-methylhistidine. It is possible that a dynamic test, which incorporates time for conversion from one amino acid to another in the intestinal cells, might perform better.
The investigators therefore propose a study of oral glutamine, arginine, and 3-methylhistidine compared with citrulline itself or placebo (glucose) as it is hypothesized that these might increase the amount of citrulline more reproducibly. An initial study in healthy subjects is required to establish whether this is true, and if so to provide a normal range prior to investigation of patients who have or who might have the short bowel syndrome, and in whom the test would be clinically useful.
In this study, the subjects will take each of the amino acids and placebo in random order. Between each 6 hour-long visit the subjects will have at least one week where they are independent of the research team and during which they can behave normally. During each visit subjects will have a sequence of blood samples from an in-dwelling venous cannula, taken before and over 6 hours after a single small oral dose of that day's amino acid given as a small volume drink. Urine will also be collected for amino acid assay.
Detailed description
Purpose and Design The purpose of the study is to determine the value of measuring citrulline after oral challenge, aiming to examine this as a function of enterocyte mass in patients with short bowel syndrome. The investigators hope to accumulate sufficient preliminary data in order to develop a new biochemical test for assessing absorption in future patient groups.
All subjects will provide written informed consent prior to their inclusion in the study. The study will be performed in accordance with International Conference on Harmonisation Guidelines for Good Clinical Practice (ICH GCP), the Helsinki Declaration and national regulations. Information about the study will be provided during one-on-one interviews with the help of a summary brochure which will be given to all potential subjects.
The study has been considered by the UK Medicines Agency, Medicines and Healthcare products Regulatory Agency (MHRA), and they agree that it is not a clinical trial of an investigational medicinal product.
Recruitment
- Potential participants will be identified by the investigator's team. The sources will include hospital and investigator databases.
- If permitted, advertisements will be posted for this study on University College London (UCL) electronic news sites, disseminated via UCL staff and student emails, with fliers to be posted on physical notice boards at UCL. Direct invitations from the researchers may also be attempted.
- Healthy volunteers will be offered £7.85/hour for their participation in this study.
Consent Written informed consent will be obtained before any study-specific procedures are carried out.
All participants will be free to withdraw from the study at any time.
Risk, burdens and benefits Apart from the small risks associated with venous access the study is expected to be without important hazard. The agents to be administered are essentially constituents of the normal diet.
There is no expectation that participants will benefit from being in this study.
Confidentiality All data provided to the sponsor or designee will be identified only by subject number or initials, thereby ensuring that the subject's identity remains unknown.
What will happen at the end of the study? Participants will be given a summary of the key results and the opportunity for further discussion on request.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Citrulline | Experimental | Dietary Supplement: Amino Acid Supplement - One doseCitrulline is a non-protein amino acid that is present in substantial amounts in watermelon (Citrullus vulgaris), with a mean content of 2.1 mg/g fresh weight, ranging from 0.5 to 3.6 mg/g according to variety. The oral dose can reach 20 g, which was administered orally in the present study in one single dose, followed by a washout period of one week Amino Acid Supplement - One dose |
| Glutamine | Experimental | Dietary Supplement: Amino Acid Supplement - One doseL-glutamine is a protein amino acid found in proteins of all life forms. It is classified as a semi-essential or conditionally essential amino acid. This means that under normal circumstances the body can synthesize sufficient l-glutamine to meet physiological demands. However, there are conditions where the body cannot do so. Recently, l-glutamine has come to be regarded as one of the most important of the amino acids when the body is subjected to such metabolic stress situations as trauma (including surgical trauma), cancer, sepsis and burns. In the present study, glutamine was administered orally in one single dose of 20 g, followed by a washout period of one week. Amino Acid Supplement - One dose |
| Arginine | Experimental | Dietary Supplement: Amino Acid Supplement - One doseArginine was administered orally in 20 g for one single dose, followed by a washout period of 1 week. Amino Acid Supplement - One dose |
| 3-Methyl-Histidine | Experimental | Dietary Supplement: 3-MethylhistidineThis amino acid is made by methylation of the actin and myosin peptide chains in the muscle. Metabolism after intravenous administration of L-3-methylhistidine involves excretion in the urine of 75% of the administered dose in 24 h and 95% in 48 h. 3-Methyl-Histidine was administered orally in 120 mg for one single dose, followed by a washout period of 1 week. |
| Placebo | Placebo comparator | Dietary Supplement: Amino Acid Supplement - One doseDextrose (glucose) was used in a dose of 20 g in this study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy volunteers fasted for at least 12 hours
- Males and females aged at least 18
Key exclusion criteria (4 listed)
- Consumption of coffee or alcohol within 12 hours
- Pregnancy
- Use of any regular medication
- Any significant past medical history
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amino Acid Supplement - One dose20gr | Dietary supplement | Arginine, Citrulline, Glutamine, Placebo |
| 3-Methylhistidine120mgr | Dietary supplement | 3-Methyl-Histidine |
Primary outcome
Area Under the Curve (AUC) for citrulline
Time frame: predose, 15,30,45,60,90,120,180,360 minutes post-dose
The primary end point for this study will be the Area Under the Curve (AUC) for citrulline after each oral load. This is the fraction of the administered dose that reaches the systemic circulation. Bioavailability is 100% for intravenous injection. It varies for other routes depending on incomplete absorption, first pass hepatic metabolism etc. Thus one plots plasma concentration against time, and the bioavailability is the AUC. The analysis of this continuous pharmacokinetic parameter will be performed on the plasma concentration-time data, using Statistical Package for the Social Sciences (SPSS) 17.0, Stata 10.0, Statistical Analysis System (SAS) and Sigma Plot.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alastair Forbes, MD, FRCP principal investigator
University College London, Centre for Gastroenterology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Amino Acid Supplement - One dose and 3-Methylhistidine in people with Intestinal Diseases, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) for citrulline (time frame: predose, 15,30,45,60,90,120,180,360 minutes post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2016.