Novel Type 2 Diabetes Mellitus Preventive Therapies

Study Overview
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Brief Summary
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Over the past two decades, type 2 diabetes mellitus (T2DM) has emerged from relative obscurity to become one of the most serious complications of obesity in Hispanic obese populations, especially among those with a family history of T2DM. Few therapies have demonstrated long term efficacy in combating obesity and risk of T2DM in youth. Given the emerging evidence that glutamine and leucine (building blocks of protein) may affect energy partition and thus diabetes risk, and that the relationship of glutamine and diabetic risk has been further evaluated in one adult observational cohort study but data on leucine are lacking, we plan to conduct a clinical trial to determine the efficacy of glutamine to reduce insulin resistance, a diabetes risk factor. The primary specific aim of the research plan is to conduct a randomized, double-blind, placebo controlled, clinical trial to test the efficacy of 6 months supplements of glutamine in reducing biomarkers for insulin resistance and weight gain among 56 obese Hispanic adolescents age 12-19 years with a BMI at or above the 95th percentile and a family history of T2DM. At the end of the grant period, we will have obtained preliminary data to plan pivotal clinical trials of glutamine coupled with or without lifestyle changes.

Detailed Description
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Because of recruitment difficulties the design was modified several times until April 2013 when we were able to increase recruitment. The following changes were made from initial to final study design: Study moved from Clinical and Translational Science Institute (CTSI) to clinical setting (Nutrition and Fitness for Life Clinic) Ages eligible expanded from 12-19 years old to 12-19.9 years old Ethnicity/Race expanded from Hispanic only to include all races/ethnicities Patients without a past family history of T2DM were made eligible Study period was shortened from 6 months to 12-14 weeks Number of required visits were reduced from 5 visits to 3 visits (all of which took place during regularly scheduled clinic appointments) Open labeled but still randomized Those in the Glutamine arm were provided lifestyles change intervention Glycosylated hemoglobin (A1C) used instead of fasting Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) Non-fasting blood draw rather than a fasting blood draw was instituted

Official Title
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Novel Type 2 Diabetes Mellitus Preventive Therapies

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Glutamine (Pharmacological doses)
* Behavioral: Lifestyle change


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI (k/m2) >= 95th percentile; Weight 150 - 400 pounds; Language: English or Spanish (The PI speaks both English and Spanish fluently). Exclusion Criteria: History of T2DM; Prior or current drug treatmeant that would effect diabetes risk Use of prescription strength glucocorticoids within three months before screening, History of syndrome or medical disorder associated with significant obesity; Serum creatinine >1.2 mg/dL; Alanine transaminase (ALT) or Aspartate aminotransferase (AST) >90 international units (IU)/L (= 3 X normal limits); Total bilirubin >2.5 time the upper limit of normal; History of moderate to extreme physical activity, past or current pregnancy; 9 .Use of illegal/illicit drugs; 10. Unable to comply with the protocol; 11. Any other serious disease determined by the clinician as potential study risk for the patient. 12. Have kidney or liver disorders, or conditions resulting in ammonia accumulation 13. Take Lactulose 14. Are allergic to monosodium glutamate (MSG), glutamine, or Crystal Light 15. Have manic episodes (mental illness) 16. Take medications to prevent seizures 17. Take any glutamine, supplement with glutamine, hypoglycemiants, anticonvulsivant, ADHD medications, antilipidemiants, or thyroid hormone 18. Participation in a weight loss program or use of weight loss medications within six months of screening that has resulted in 5% or more weight loss

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glutamine + Lifestyle change<br>Glutamine 30 grams/day X 12-14 weeks, Lifestyle change | Drug: Glutamine (Pharmacological doses)<br>* 30 grams/day of glutamine for 12-14 months<br>* Other names: NutreStore;Behavioral: Lifestyle change<br>* Lifestyle change as recommended by Registered Dietitian<br>|
| Placebo Comparator: No glutamine + Lifestyle change<br>Lifestyle change | Behavioral: Lifestyle change<br>* Lifestyle change as recommended by Registered Dietitian<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight gain |  | 12-14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in A1C |  | 12-14 weeks |