Dietary Intake of Tryptophan and Metformin Response

Study Overview
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Brief Summary
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This study will examine the influence of dietary intake of tryptophan on response to metformin. The investigators hypothesize that dietary tryptophan alteration will influence metformin response.

Conditions
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Metformin Response, Fasting Glucose, Tryptophan Concentration, Metformin Concentration, Diet Tolerability

Intervention / Treatment
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* Drug: Metformin
* Other: Low tryptophan diet
* Other: High tryptophan diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy adult male or non-pregnant female volunteers (age 20-40) able and willing to give consent Exclusion Criteria: Age less than 20 or greater than 40 Women who are pregnant, nursing, or at risk of becoming pregnant Body mass index (BMI) less than 20 or greater than 28 Changes of more than 5 pounds in weight (increase or decrease) during the month prior to enrollment in the study Participation in more than 300 minutes of exercise per week during the month prior to enrollment in the study Known diabetes or pre-diabetes (based on prior diagnoses, use of medications to lower glucose; or fasting blood glucose > 100mg/dL at screening) Untreated hypertension (defined as systolic blood pressure > 140mmHg and diastolic blood pressure > 90mmHg) Current or past mood disorder, including major depression, anxiety, or bipolar disorder Conditions causing intestinal malabsorption, including celiac disease or a history of intestinal or gastric bypass surgery History of liver disease and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times upper limit of normal (ULN) Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation Currently taking or intending to take during the study duration any medication known to affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones Use of medications and herbal or vitamin supplements during the study Contraindications to safe use of metformin, including planned radiologic or angiographic study requiring contrast within one week of the study completion Objection to taking metformin Participation in any other interventional study during the study duration Use of nicotine-containing products, including inhaled, chewed, or patches during the study. Use of drugs of abuse. Restrictions that prevent adherence to standardized meals or unwillingness to adhere to a pre-specified meal plan, including abstinence from alcohol and limitation of caffeine intake to one drink daily.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low tryptophan diet<br>2 days of a low tryptophan diet | Drug: Metformin<br>* 2 doses of 500 mg metformin given approximately 12 hrs apart<br>Other: Low tryptophan diet<br> <br> |
| Experimental: High tryptophan diet<br>2 days of a high tryptophan diet | Drug: Metformin<br>* 2 doses of 500 mg metformin given approximately 12 hrs apart<br>Other: High tryptophan diet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in fasting glucose |  | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in tryptophan concentration |  | 2 days |