HealthyNCT04142294
Safety of Graded-Dose of Histidine in Humans
A study testing Histidine in people with Healthy, run by Cornell University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Histidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Sep 2017to 31 Aug 2019
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy young males and females aged 21-50 y.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Human Metabolic Research Unit
Ithaca, New York, 14853
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Histidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HistidineDietary supplement
ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| 4 g / day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day. Receives: Dietary Supplement: Histidine |
| 8 g / day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day Receives: Dietary Supplement: Histidine |
| 12 g /day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day Receives: Dietary Supplement: Histidine |
| 16 g /day histidine | Experimental | 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 Receives: Dietary Supplement: Histidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in concentration of zinc in mg/ml
The safety of histidine supplementation at each dose is monitored through blood markers of zinc
Measured: at week 0 and 4 of each dose
Change in concentration of liver enzymes (ALT, ALP, and AST) in Units per Liter
The safety of histidine supplementation at each dose is monitored through circulating liver enzymes
Measured: at weeks 0 (washout), 2 and 4 of each dose
Change in body weight in kilograms
The safety of histidine supplementation at each dose is monitored through changes in weight
Measured: at weeks 0 (washout), 2 and 4 of each dose
Change in concentration of total protein and albumin in g/dl
The safety of histidine supplementation at each dose is monitored through circulating total protein and albumin
Measured: at weeks 2 and 4 of each dose
Change in concentration of blood urea nitrogen, Creatinine, bilirubin and glucose each in mg/gL
The safety of histidine supplementation at each dose is monitored through circulating blood urea nitrogen, Creatinine, bilirubin and glucose
Measured: at weeks 0 (washout), 2 and 4 of each dose
Change in concentration of C-reactive protein mg/L
The safety of histidine supplementation at each dose is monitored through circulating CRP
Measured: at weeks 0 (washout), 2 and 4 of each dose
HgbA1c in %
The safety of histidine supplementation at each dose is monitored through circulating HgbA1c
Measured: at week 4 of each dose
Change in heart rate in beats per minute
The safety of histidine supplementation at each dose is monitored through heart rate
Measured: weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
Change in systolic and diastolic blood pressures in mmHG
The safety of histidine supplementation at each dose is monitored through blood pressure
Measured: weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose
Secondary outcomes (5)
Change in hours of sleep
The effects of histidine will be assessed with changes in sleep pattern as determined using a subjective measurement tool
Measured: 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
The effects of histidine will be assessed with changes dietary intake as determined with 4 day food records
Measured: week 0 to 4 of each dose
Change in physical activity measured in steps per day
The effects of histidine will be assessed with changes in physical activity patterns using an Actigraph
Measured: week 0 to 4 of each dose
Change in subjective mood measured in arbitrary units
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.
Measured: week 0 to 4 of each dose
Change in subjective desire to eat measured in arbitrary units
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.
Measured: week 0 to 4 of each dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start21 Sep 2017
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Histidine supplementation trial, non-randomized, sequential delivery of graded doses of the amino acid histidine. All participants serve as their own controls. Following baseline measurements, subjects ingest encapsulated high quality histidine for four continuous weeks at graded doses of 4, 8 and 12 g/day. A forth dose at 16 g/day is assessed if no adverse outcomes are observed for the three graded doses. Histidine doses are suggested based on experience with other amino acids (relative difference of average intake and metabolic limits). Each dose is followed by a 3-week minimum recovery period. During the recovery period, subjects will continue to be monitored (vitals and weight) but no supplementation is consumed. At the conclusion of each washout period, before the start of the next dose, subjects provide a blood sample, vitals (blood pressure and heart rate), weight, 4-day diet record, sleep log, hunger and satiety VAS, mood VAS, and physical activity monitoring.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04142294
- Sponsor's protocol ID
- 83676/A001
- Status last verified
- Jan 2022
- First submitted
- 30 Oct 2018
- Last updated
- 7 Feb 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gheller ME, Vermeylen F, Handzlik MK, Gheller BJ, Bender E, Metallo C, Aydemir TB, Smriga M, Thalacker-Mercer AE. Tolerance to graded dosages of histidine supplementation in healthy human adults. Am J Clin Nutr. 2020 Nov 11;112(5):1358-1367. doi: 10.1093/ajcn/nqaa210.
PubMed 32766885
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Graded-Dose of Histidine as Determined by Circulating Analytes, Sleep Records, Physical Activity, Anthropometric Measurements, and Mood
- ClinicalTrials.gov ID
- NCT04142294
- Acronym / sponsor ID
- 83676/A001
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Cornell UniversityUniversity, hospital or other
- Study start
- 21 Sep 2017 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 29 Oct 2019 (actual)
- 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.
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.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Histidine supplementation trial, non-randomized, sequential delivery of graded doses of the amino acid histidine. All participants serve as their own controls. Following baseline measurements, subjects ingest encapsulated high quality histidine for four continuous weeks at graded doses of 4, 8 and 12 g/day. A forth dose at 16 g/day is assessed if no adverse outcomes are observed for the three graded doses. Histidine doses are suggested based on experience with other amino acids (relative difference of average intake and metabolic limits). Each dose is followed by a 3-week minimum recovery period. During the recovery period, subjects will continue to be monitored (vitals and weight) but no supplementation is consumed. At the conclusion of each washout period, before the start of the next dose, subjects provide a blood sample, vitals (blood pressure and heart rate), weight, 4-day diet record, sleep log, hunger and satiety VAS, mood VAS, and physical activity monitoring.
| Arm | Type | Receives |
|---|---|---|
| 4 g / day histidine | Experimental | Dietary Supplement: Histidinesubjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day. |
| 8 g / day histidine | Experimental | Dietary Supplement: Histidinesubjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day |
| 12 g /day histidine | Experimental | Dietary Supplement: Histidinesubjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day |
| 16 g /day histidine | Experimental | Dietary Supplement: Histidinesubjects 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 |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- healthy young males and females aged 21-50 y.
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Histidineingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks | Dietary supplement | 12 g /day histidine, 16 g /day histidine, 4 g / day histidine, 8 g / day histidine |
Primary outcome
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
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
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
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
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
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
HgbA1c in %
Time frame: at week 4 of each dose
The safety of histidine supplementation at each dose is monitored through circulating HgbA1c
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
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
5 secondary outcomes
Change in hours of sleep
Time frame: 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
Change in physical activity measured in steps per day
Time frame: week 0 to 4 of each dose
Change in subjective mood measured in arbitrary units
Time frame: 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
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 7 Feb 2022.
- Derived from this study: PubMed 32766885Gheller ME, Vermeylen F, Handzlik MK, Gheller BJ, Bender E, Metallo C, Aydemir TB, Smriga M, Thalacker-Mercer AE. Tolerance to graded dosages of histidine supplementation in healthy human adults. Am J Clin Nutr. 2020 Nov 11;112(5):1358-1367. doi: 10.1093/ajcn/nqaa210.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Histidine in people with Healthy, run by Cornell 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 1 inclusion and 11 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 7 Feb 2022. 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?
Change in concentration of zinc in mg/ml (time frame: at week 0 and 4 of each dose). The study lists 9 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 NCT04142294, 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 7 Feb 2022.