HealthyMetNCT02566434
Methionine Tolerance in Healthy Human Adults
A study testing methionine in people with Healthy, run by Texas A&M University at 1 site in United States.
Trial summary
Participants will receive four different doses of methionine through four month long interventions with a two week wash-out period in between intervention. The dose will increase with each intervention. Read more about this study
- Who is it for?
- Ages 40 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- methionine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Oct 2017
- 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 40 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Must be a healthy male or female according to the investigator's or appointed staff's judgment
- Age 40 - 79 years.
- Must be willing to lay in bed for 4 hours on the long study days (LD)
- Have a stable body weight within the past 3 months (< 5% change)
Who cannot join
- History of cardiovascular disease
- Metabolic diseases including hepatic or renal disorder
- Presence of acute illness or metabolically unstable chronic illness
- Unwilling to stop taking nutritional supplements containing proteins or free amino acids within 5 days of the first study day until study completion
- Have not taken or participated in any nutritional supplement study program within the past 4 weeks
- Any other condition according to the PI or nurse that would interfere with the study or safety of the subject or influence the results
- Pregnancy
- Unwilling to comply with any other rules set forth in the Informed Consent Form
Trial locations and contacts
1 site in 1 country.
United States1 site
Texas A&M University-CTRAL
College Station, Texas, 77845-4253
About this study
Participants will receive four different doses of methionine through four month long interventions with a two week wash-out period in between intervention. The dose will increase with each intervention. Two visits during each intervention will also involve receiving stable isotope infusion to determine the metabolism of methionine in the body. Participants will also be monitored via blood work and questionnaires regarding overall health.
Read the detailed description
Study subjects: Healthy volunteers (40 - 79 years) will be included in the study. Informed consent will be obtained before any study related procedures will be performed. All subjects will be extensively screened by research nurses / physician. Exclusion criteria are any condition that interfere with the definition 'healthy" according to the study physician's judgement based on medical history, lab testing, use of medication, and physical exam.
Study design: To establish the Upper Level of Safe intake (USLI) of methionine intake, it is essential to create a dose-response approach of possible negative effects of methionine. To define the Lowest-Observed-Adverse-Effect Level (LOAEL), the investigators suggest a 4 weeks intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day. Pure methionine will be provided by ICAAS. The 4-week intervention period is based on a study in pigs (6). Methionine will be consumed in 3 daily doses. Participants will be advised about their daily dietary intake during the study. Besides the screening visit, each subjects will come back for up to 13 study visits (up to 5 Short study Days (SD, approx. 30 min) and 8 Long study Days (LD, approx. 5 h). On all study days (both SD and LD) the investigators will check parameters of toxicity and measure metabolites of methionine catabolism on the day before each dose intervention, during intervention (2 weeks after the start of each dose intervention; range: +/- 3 days), on the last day of each dose intervention, and 2 weeks after the last dose intervention. Because methionine as a dietary supplement clearly rises a safety issue, we will conduct this experiment in steps. First, subjects will receive the 10 mg/kg body weight/day. The investigators then will analyse all parameters of toxicity, interpret the data and when there are no safety concerns, continue with the next intake level. The study will be stopped at the level when there are apparent safety concerns.
The study will take place at the research facility of the Center for Translational Research on Aging and Longevity (CTRAL), Texas A\&M University. The subject will be asked to arrive in the fasted state on both the screening and all study days. On the screening day, body weight and height will be measured and Dual-energy X-ray absorptiometry (DXA) will be performed to measure body composition. On both SD and LD a medical interview will be performed and a toxicity questionnaire completed (see attached protocol). Furthermore on a SD two blood samples will be taken (up to 30 ml). On a LD, one catheter will be inserted in the peripheral vein of an arm for blood sampling (18 samples in total, up to 80 ml per LD) and questionnaires related to cognition, health status and well being may or may not be completed by the subject (see attached protocol). After a baseline blood sample is taken, a stable isotope pulse is provided through the same line. The baseline sample will be used to test toxicity parameters in blood, plasma homocysteine concentration, the plasma concentrations of products of the methionine degrading transamination and sulfoxidation route, and to establish background enrichment of stable isotopes. Samples obtained after the pulse will provide information about transmethylation of methionine, and GSH synthesis. Subjects will be called every week to check compliance regarding supplement intake and to answer questions regarding health and well-being. Subjects who discontinue the study during the study will not be replaced.
- Conditions
- Healthy
- Being tested
- methionine
- Keywords
- Dietary Supplements
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methionineDietary supplement
4 weeks intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day.
| Study group | Role | What they receive |
|---|---|---|
| Methionine | Experimental | All participants will consume free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day for the duration of a 4-week intervention period. Participants will cease intake when signs of toxicity are measured in blood work. Receives: Dietary Supplement: methionine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Function Panel--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--25 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--25mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--25 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Secondary outcomes (12)
Complete Aminogram--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--10 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--25 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--25 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--25 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--50 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--100 mg/kg body weight dose
Measured: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2015 (estimated)
- Study startJul 2015
- Primary completionApr 2016
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Texas A&M University
- Sponsor type
- University, hospital or other
- Collaborators
- International Council on Amino Acid Science
- Responsible party
- Principal investigator, Marielle PKJ Engelen, PhD, Texas A&M University
- Investigators
- Marielle Engelen, Study director, Texas A&M University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02566434
- Sponsor's protocol ID
- 2014-0800
- Acronym
- Met
- Status last verified
- Sep 2018
- First submitted
- 21 Sep 2015
- Last updated
- 26 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Deutz NE, Simbo SY, Ligthart-Melis GC, Cynober L, Smriga M, Engelen MP. Tolerance to increased supplemented dietary intakes of methionine in healthy older adults. Am J Clin Nutr. 2017 Aug;106(2):675-683. doi: 10.3945/ajcn.117.152520. Epub 2017 Jun 21.
PubMed 28637772
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methionine Tolerance in Healthy Human Adults
- ClinicalTrials.gov ID
- NCT02566434
- Acronym / sponsor ID
- Met / 2014-0800
- Conditions
- Healthy
- Keywords
- Dietary Supplements
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Texas A&M UniversityUniversity, hospital or other
- Collaborators
- International Council on Amino Acid Science
- Study start
- Jul 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 2 Oct 2015 (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.
Participants will receive four different doses of methionine through four month long interventions with a two week wash-out period in between intervention. The dose will increase with each intervention. Two visits during each intervention will also involve receiving stable isotope infusion to determine the metabolism of methionine in the body. Participants will also be monitored via blood work and questionnaires regarding overall health.
Detailed description
Study subjects: Healthy volunteers (40 - 79 years) will be included in the study. Informed consent will be obtained before any study related procedures will be performed. All subjects will be extensively screened by research nurses / physician. Exclusion criteria are any condition that interfere with the definition 'healthy" according to the study physician's judgement based on medical history, lab testing, use of medication, and physical exam.
Study design: To establish the Upper Level of Safe intake (USLI) of methionine intake, it is essential to create a dose-response approach of possible negative effects of methionine. To define the Lowest-Observed-Adverse-Effect Level (LOAEL), the investigators suggest a 4 weeks intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day. Pure methionine will be provided by ICAAS. The 4-week intervention period is based on a study in pigs (6). Methionine will be consumed in 3 daily doses. Participants will be advised about their daily dietary intake during the study. Besides the screening visit, each subjects will come back for up to 13 study visits (up to 5 Short study Days (SD, approx. 30 min) and 8 Long study Days (LD, approx. 5 h). On all study days (both SD and LD) the investigators will check parameters of toxicity and measure metabolites of methionine catabolism on the day before each dose intervention, during intervention (2 weeks after the start of each dose intervention; range: +/- 3 days), on the last day of each dose intervention, and 2 weeks after the last dose intervention. Because methionine as a dietary supplement clearly rises a safety issue, we will conduct this experiment in steps. First, subjects will receive the 10 mg/kg body weight/day. The investigators then will analyse all parameters of toxicity, interpret the data and when there are no safety concerns, continue with the next intake level. The study will be stopped at the level when there are apparent safety concerns.
The study will take place at the research facility of the Center for Translational Research on Aging and Longevity (CTRAL), Texas A\&M University. The subject will be asked to arrive in the fasted state on both the screening and all study days. On the screening day, body weight and height will be measured and Dual-energy X-ray absorptiometry (DXA) will be performed to measure body composition. On both SD and LD a medical interview will be performed and a toxicity questionnaire completed (see attached protocol). Furthermore on a SD two blood samples will be taken (up to 30 ml). On a LD, one catheter will be inserted in the peripheral vein of an arm for blood sampling (18 samples in total, up to 80 ml per LD) and questionnaires related to cognition, health status and well being may or may not be completed by the subject (see attached protocol). After a baseline blood sample is taken, a stable isotope pulse is provided through the same line. The baseline sample will be used to test toxicity parameters in blood, plasma homocysteine concentration, the plasma concentrations of products of the methionine degrading transamination and sulfoxidation route, and to establish background enrichment of stable isotopes. Samples obtained after the pulse will provide information about transmethylation of methionine, and GSH synthesis. Subjects will be called every week to check compliance regarding supplement intake and to answer questions regarding health and well-being. Subjects who discontinue the study during the study will not be replaced.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methionine | Experimental | Dietary Supplement: methionineAll participants will consume free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day for the duration of a 4-week intervention period. Participants will cease intake when signs of toxicity are measured in blood work. |
Who may qualify
- Ages
- 40 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Must be a healthy male or female according to the investigator's or appointed staff's judgment
- Age 40 - 79 years.
- Must be willing to lay in bed for 4 hours on the long study days (LD)
- Have a stable body weight within the past 3 months (< 5% change)
Key exclusion criteria (8 listed)
- History of cardiovascular disease
- Metabolic diseases including hepatic or renal disorder
- Presence of acute illness or metabolically unstable chronic illness
- Unwilling to stop taking nutritional supplements containing proteins or free amino acids within 5 days of the first study day until study completion
- Have not taken or participated in any nutritional supplement study program within the past 4 weeks
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 |
|---|---|---|
| methionine4 weeks intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day. | Dietary supplement | Methionine |
Primary outcome
Hepatic Function Panel--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--25 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--25mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--25 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Hepatic Function Panel--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Metabolic Renal Function Panel--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Blood Count (CBC) With Differential--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
12 secondary outcomes
Complete Aminogram--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--10 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--25 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--25 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--25 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--50 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Complete Aminogram--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Glutathione ratio--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
Plasma Homocysteine concentration--100 mg/kg body weight dose
Time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
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 26 Sep 2018.
- Derived from this study: PubMed 28637772Deutz NE, Simbo SY, Ligthart-Melis GC, Cynober L, Smriga M, Engelen MP. Tolerance to increased supplemented dietary intakes of methionine in healthy older adults. Am J Clin Nutr. 2017 Aug;106(2):675-683. doi: 10.3945/ajcn.117.152520. Epub 2017 Jun 21.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Marielle Engelen study director
Texas A&M University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing methionine in people with Healthy, run by Texas A&M University at 1 site in United States.
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 4 inclusion and 8 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 26 Sep 2018. 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 States. 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. 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?
Hepatic Function Panel--10 mg/kg body weight dose (time frame: participants will be followed for the duration of the dose intervention, an expected average of 4 weeks). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02566434, which also lists 1 linked publication.
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 26 Sep 2018.