- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02566434
Methionine Tolerance in Healthy Human Adults (Met)
Study Overview
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Texas
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College Station, Texas, United States, 77845-4253
- Texas A&M University-CTRAL
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Methionine
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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
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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
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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
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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
|
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
|
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
|
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
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participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
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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
|
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
|
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
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participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
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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
|
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
|
participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
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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
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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
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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
|
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
|
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
|
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
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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
|
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
|
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
|
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
|
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
|
participants will be followed for the duration of the dose intervention, an expected average of 4 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Marielle Engelen, Texas A&M University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2014-0800
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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