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Glucose ToleranceNCT03872557

Modulating Glucose Tolerance With Dietary Tyrosine

A study testing Tyrosine (TYR) Supplementation in people with Glucose Tolerance, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Metabolic or Bariatric surgery is an effective treatment for type 2 diabetes mellitus (T2DM) diabetes associated with obesity. There remain some questions about the biochemical mechanism that drive how these surgeries work to reverse hyperglycemia. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Glucose Tolerance
What is being tested?
Tyrosine (TYR) Supplementation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
7 Aug 2019to 24 Jan 2020
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 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult
  1. Inclusion Criteria
  2. Capable of giving written as well as oral informed consent.
  3. A fasting plasma glucose level (FPG) < 126 mg/dL (< 7.0 mmol/L) and an Hb1ac in the 5.7-6.4 % range.
  4. BMI in the range of 18-45 kg/m2.
  5. Normal Complete blood count (CBC), renal and liver function tests. ii. Exclusion Criteria:
  6. Any diabetes medication within previous three (3) months.
  7. Fasting plasma Glucose (FPG) >126 mg/dl or HbA1c > 6.4%
  8. Current use (or within 6 months) of antipsychotic, anti-anxiety, or antidepressant medications (e.g. monoamine oxidase (MAO) inhibitors, 5-Hydroxytryptophan (5HT) inhibitors, tricyclic antidepressants, L-DOPA), reserpine, β-2-receptor agonists (e.g., terbutaline), steroids, weight loss medication, anticoagulant medication, over-the-counter nutritional supplements other than standard vitamin and mineral supplements
  9. History of Phenylketonuria or other inherited disorders of amino acid metabolism.
  10. History of movement disorder such as Parkinson's disease or Huntington's disease
  11. Cardiovascular, renal, pulmonary, gastrointestinal, migraines or other medical conditions deemed significant by investigators
  12. History of/ or psychiatric illness such as major depression, bipolar disease, anxiety or schizophrenia.
  13. History of bariatric surgery with the exception of gastric band if the band has been removed
  14. Female of child-bearing age, currently pregnant, breastfeeding or not using a form of birth control.
  15. Previous or current use of cocaine, methamphetamine, ecstasy (3-4 methylenedioxymethamphetamine (MDMA))
  16. Current daily intake of caffeine >500 mg/day (>4-5 cups of coffee; >10 12-oz cans of soda)
  17. Consumption of more than 1 alcoholic drink per day or smoking more than 5 cigarettes/day.
  18. Systolic Blood Pressure (SBP) > 150 mmHg; Diastolic Blood Pressure (DBP) > 100 mmHg.
  19. Recent history (in the past three months) of more than a 3% gain or loss in body wt.
  20. Difficulty in swallowing capsules.
  21. Concurrent use of antacids or proton pump inhibitors (e.g.,Prilosec Prevacid, dexilant, Aciphex, Protonix, Nexium, Vimovo, Zegerid)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Irving Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Metabolic or Bariatric surgery is an effective treatment for type 2 diabetes mellitus (T2DM) diabetes associated with obesity. There remain some questions about the biochemical mechanism that drive how these surgeries work to reverse hyperglycemia. In the proposed human studies, the investigators will test the hypothesis that the amino acid tyrosine is a key metabolite in regulating blood sugar levels and that manipulation of the amount tyrosine supplied by nutrition is able to achieve some of the metabolic benefits seen in the early post-surgical period following bariatric surgery. The central hypothesis is that that the tyrosine content of the meal challenge affects post-prandial intestinal and plasma dopamine and levodopa and L-3,4-dihydroxyphenylalanine (L-DOPA) levels, which, in turn, impact β-cell insulin secretion and glucose excursions. The investigators now propose to characterize the possible effects of manipulating dopamine and L-DOPA levels in the gut and plasma on glucose tolerance, insulin secretion, and insulin sensitivity in healthy volunteers with a range of body mass indexes (BMIs).

Read the detailed description

Several biochemical mechanisms explaining how Roux-en-Y Gastric Bypass (RYGB) provides an effective treatment for obesity associated type 2 diabetes mellitus (T2DM) and improves hyperglycemia independently of weight loss have been proposed. Two are of particular interest; a) the hindgut hypothesis suggesting that nutrient delivery to the distal intestine drives the production of "incretins" which enhance insulin secretion (e.g. glucagon-like peptide-1 (GLP-1)), and b) the foregut hypothesis, positing that foregut bypass reduces the secretion of factors (i.e. anti-incretins) that normally defend against hypoglycemia. The investigators have been actively investigating this topic and have developed a hypothesis based on past studies that they wish to test in a limited human clinical study. In addition, preclinical data suggest that there exists a gut-to-beta cell pathway, responsive to nutritional tyrosine, regulating insulin secretion, and this pathway provides a mechanism for the early postoperative improvements in hyperglycemia observed in RYGB.

Being tested
Tyrosine (TYR) Supplementation
Keywords
Glucose tolerance, Tyrosine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tyrosine (TYR) SupplementationDietary supplement

    L-Tyrosine dietary supplement will be provided as 500 mg capsules and 4 (four) 500 mg capsules are to be given before OGTT. The capsules are formed from animal gelatin, and the contents are formulated with magnesium stearate as a flow agent, but without binders, coatings or colorings and also have no added flavorings, sugars, salt, artificial sweeteners, preservatives or salicylates. The capsules are to be administered with less than eight ounces of water to minimize dilution of gastric acidity.

Study groups in NCT03872557
Study groupRoleWhat they receive
Tyrosine (TYR) depletion, then oral TYRActive comparatorTYR supplementation: Subjects will be directed to avoid consumption of L-DOPA and TYR enriched foods for 48 hours before oral glucose tolerance test (OGTT). On the evening prior to OGTT, subjects will substitute normal meal and snack for three prepackaged tyrosine-phenylalanine-free liquid meals. Visit 2. Placement of intravenous catheter for the collection of serial blood samples and an OGTT with supplementation with oral tyrosine supplement. To supplement the OGTT with Tyrosine, the contents of four (4) L-Tyrosine 500 mg capsule are given 45 minutes before the oral glucose solution is administered. The capsules are to be administered with less than eight ounces of water to minimize dilution of gastric acidity.
Receives: Dietary Supplement: Tyrosine (TYR) Supplementation
TYR depletion, then no oral TYRNo interventionSubjects will be directed to avoid consumption of L-DOPA and TYR enriched foods for 48 hours before OGTT. On the evening prior to OGTT, subjects will substitute normal meal and snack for three prepackaged tyrosine-phenylalanine-free liquid meals. Subsequent Visit 3. This visit will consist of placement of intravenous catheter for the collection of serial blood samples and an OGTT without supplementation with oral tyrosine supplement.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Whole blood glucose level

    Glucose concentration versus time profile following glucose challenge define glucose tolerance

    Measured: Up to 120 minutes from baseline

  2. Plasma insulin concentration

    Plasma insulin concentration versus time profile following glucose challenge define glucose tolerance

    Measured: Up to 120 minutes from baseline

  3. Plasma dopamine concentration

    Plasma dopamine concentration versus time profile following glucose challenge may affect glucose tolerance

    Measured: Up to 120 minutes from baseline

  4. Plasma L-DOPA concentration

    Plasma L-DOPA concentration versus time profile following glucose challenge may affect glucose tolerance

    Measured: Up to 120 minutes from baseline

  5. L-tyrosine concentration

    Plasma L-tyrosine concentration versus time profile following glucose challenge may affect glucose tolerance

    Measured: Up to 120 minutes from baseline

  6. Plasma glucagon concentration

    Plasma glucagon concentration versus time profile following glucose challenge impacts glucose tolerance

    Measured: Up to 120 minutes from baseline

  7. Plasma GLP-1 concentration

    Plasma GLP-1 concentration versus time profile following glucose challenge impacts glucose tolerance

    Measured: Up to 120 minutes from baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2019
  2. Study start7 Aug 2019
  3. Primary completion24 Jan 2020
  4. Study completion24 Jan 2020

Resources

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
Basic science
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03872557
Sponsor's protocol ID
AAAS2124
Other IDs
R01DK104740
Status last verified
Apr 2021
First submitted
11 Mar 2019
Last updated
5 May 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Korner J, Cline GW, Slifstein M, Barba P, Rayat GR, Febres G, Leibel RL, Maffei A, Harris PE. A role for foregut tyrosine metabolism in glucose tolerance. Mol Metab. 2019 May;23:37-50. doi: 10.1016/j.molmet.2019.02.008. Epub 2019 Feb 27.

    PubMed 30876866

Questions about this trial

What is this clinical trial studying?

A study testing Tyrosine (TYR) Supplementation in people with Glucose Tolerance, run by Columbia 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?

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 5 May 2021. 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?

Whole blood glucose level (time frame: Up to 120 minutes from baseline). The study lists 7 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 NCT03872557, 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 5 May 2021.

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