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

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 4 g / day histidine
subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day.
Dietary supplement: Histidine
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
Dietary supplement: Histidine
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
Dietary supplement: Histidine
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
Dietary supplement: Histidine
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cornell University

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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