- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04142294
Safety of Graded-Dose of Histidine in Humans
January 24, 2022 updated by: Cornell University
Safety of Graded-Dose of Histidine as Determined by Circulating Analytes, Sleep Records, Physical Activity, Anthropometric Measurements, and Mood
Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management.
The current expert opinion for histidine intake is 8 and 12 mg/(kg body weight per day), an estimate that was extrapolated from the infant requirement for histidine.
Further, the clinical safety of histidine supplementation above the average dietary intake has not been determined.The overarching objectives are to 1) measure the safety of histidine supplementation and 2) measure the potential benefits of histidine at doses above the average intake and current recommendation in a healthy adult population.
Study Overview
Detailed Description
Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management.
Because of the extended period of time (>35 days) that is required to deplete body histidine pools in adults, it has not been possible to fully determine histidine requirements.
The current expert opinion for histidine intake is 8 and 12 mg/(kg body weight per day), an estimate that was extrapolated from the infant requirement for histidine.
The average intake of histidine from a normal adult diet in the U.S., Europe, and Japan was reported between 2.12 and 2.40 g/day with the 99th percentile intake in men at 50-70 years of age consuming 5.20 g/day.
The clinical safety of histidine supplementation above the average dietary intake has not been determined.
Therefore, this study will utilize graded doses of histidine that are at are moderately above the average intake to identify safety and benefits of histidine in a healthy human population.
Further, the clinical safety of histidine supplementation above the average dietary intake has not been determined.The overarching objectives are to 1) measure the safety of histidine supplementation and 2) measure the potential benefits of histidine at doses above the average intake and current recommendation in a healthy adult population.
Following the completion and review of a health history questionnaire, vitals, and a biochemical panel, participants will be deemed healthy by a nurse practitioner and able to participate.
After baseline measures are obtained, supplements (encapsulated histidine) will be provided at three graded doses (4 g/day, 8 g/day and 12 g/day) a forth dose (16 g/day) will be consumed if no adverse effects are observed at the three graded doses.
Each dose will be for 28 days followed by a three week recovery period.
At baseline, weeks 2 and 4 of supplement, and recovery a basic biochemical panel, anthropometric, urinary and serum zinc, will be conducted.
Additionally, body composition will be conducted at baseline and week 4 of each dose.
Changes in dietary intake and physical activity will be measured with 4-day food records and Actigraph activity monitors, respectively.
Changes in sleep patterns will be measured with the Pittsburgh sleep questionnaire.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
Ithaca, New York, United States, 14853
- Human Metabolic Research Unit
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 50 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
• healthy young males and females aged 21-50 y.
Exclusion Criteria:
- A body-mass index (BMI) <19.9 kg/m2 or > 29.9 kg/m2
- taking/on immunosuppressive medications or prescription anti-coagulation therapy
- pregnancy
- breastfeeding
- musculoskeletal disorder
- diabetes
- alcoholism (>11 drinks per week for women, >14 drinks per week for men) or other drug addiction
- acute illness
- inability to travel to Cornell University campus
- A blood pressure at or above 140/90
- For individuals desiring to participate in the optional biopsy, a history of a negative or allergic reaction to local anesthetic is an exclusion criteria
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 4 g / day histidine
subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day.
|
ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
|
Experimental: 8 g / day histidine
subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day
|
ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
|
Experimental: 12 g /day histidine
subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day
|
ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
|
Experimental: 16 g /day histidine
subjects ingest encapsulated high quality histidine for four continuous weeks at 16 g/day.
The 16 g /day dose will be administered if no adverse effects are observed for doses 4-12 g/day
|
ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in concentration of zinc in mg/ml
Time Frame: at week 0 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through blood markers of zinc
|
at week 0 and 4 of each dose
|
Change in concentration of liver enzymes (ALT, ALP, and AST) in Units per Liter
Time Frame: at weeks 0 (washout), 2 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through circulating liver enzymes
|
at weeks 0 (washout), 2 and 4 of each dose
|
Change in body weight in kilograms
Time Frame: at weeks 0 (washout), 2 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through changes in weight
|
at weeks 0 (washout), 2 and 4 of each dose
|
Change in concentration of total protein and albumin in g/dl
Time Frame: at weeks 2 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through circulating total protein and albumin
|
at weeks 2 and 4 of each dose
|
Change in concentration of blood urea nitrogen, Creatinine, bilirubin and glucose each in mg/gL
Time Frame: at weeks 0 (washout), 2 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through circulating blood urea nitrogen, Creatinine, bilirubin and glucose
|
at weeks 0 (washout), 2 and 4 of each dose
|
Change in concentration of C-reactive protein mg/L
Time Frame: at weeks 0 (washout), 2 and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through circulating CRP
|
at weeks 0 (washout), 2 and 4 of each dose
|
HgbA1c in %
Time Frame: at week 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through circulating HgbA1c
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at week 4 of each dose
|
Change in heart rate in beats per minute
Time Frame: weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through heart rate
|
weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
|
Change in systolic and diastolic blood pressures in mmHG
Time Frame: weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
|
The safety of histidine supplementation at each dose is monitored through blood pressure
|
weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in hours of sleep
Time Frame: week 0 to 4 of each dose
|
The effects of histidine will be assessed with changes in sleep pattern as determined using a subjective measurement tool
|
week 0 to 4 of each dose
|
Change in dietary intake of energy, macronutrients, and amino acids measured in kcals and g/day with 4 day food record
Time Frame: week 0 to 4 of each dose
|
The effects of histidine will be assessed with changes dietary intake as determined with 4 day food records
|
week 0 to 4 of each dose
|
Change in physical activity measured in steps per day
Time Frame: week 0 to 4 of each dose
|
The effects of histidine will be assessed with changes in physical activity patterns using an Actigraph
|
week 0 to 4 of each dose
|
Change in subjective mood measured in arbitrary units
Time Frame: week 0 to 4 of each dose
|
The effects of histidine will be assessed with changes in mood as determined using a subjective visual analog scale.
100 mm line is anchored by two opposing statements.
The higher number the greater the mood.
|
week 0 to 4 of each dose
|
Change in subjective desire to eat measured in arbitrary units
Time Frame: week 0 to 4 of each dose
|
The effects of histidine will be assessed with changes in desire to eat will be determined using a visual analog scale.
100 mm line is anchored by two opposing statements.
The greater the number the stronger the desire.
|
week 0 to 4 of each dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 21, 2017
Primary Completion (Actual)
August 31, 2019
Study Completion (Actual)
August 31, 2019
Study Registration Dates
First Submitted
October 30, 2018
First Submitted That Met QC Criteria
October 25, 2019
First Posted (Actual)
October 29, 2019
Study Record Updates
Last Update Posted (Actual)
February 7, 2022
Last Update Submitted That Met QC Criteria
January 24, 2022
Last Verified
January 1, 2022
More Information
Terms related to this study
Other Study ID Numbers
- 83676/A001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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