Glutamine and Insulin Sensitivity in Type I Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Dominique Darmaun, Nemours Children's Clinic
ClinicalTrials.gov Identifier:
NCT01467063
First received: November 2, 2011
Last updated: May 2, 2013
Last verified: May 2013
  Purpose

Insulin is crucial to help the body metabolize ('burn') sugar (glucose). Even though juvenile (type 1) diabetes (T1D) is primarily due to the lack of insulin, patients with T1D tend to become less sensitive to insulin, particularly during adolescence.

The overall objective of this project is to gain further insight into the possible benefits of supplementation with glutamine (GLN), a natural dietary amino acid, enhancing insulin sensitivity in adolescents with T1D. To elucidate the impact of glutamine, the investigators will use a method called the 'euglycemic, hyperinsulinemic clamp': it consists of giving an IV drip of insulin, while the drop in blood sugar is prevented by giving variable, precisely measured amounts of glucose by vein: the amount of glucose required to prevent a drop in blood sugar reflects the body's sensitivity to insulin. The investigators will also give an IV drip of glucose and arginine (a building block of protein) 'tagged' with non-radioactive isotopes to better understand how glutamine may work. This procedure will be performed in 2 groups of 10 adolescents in the morning either after a strenuous exercise performed the previous afternoon (group 1; n=10), or after a sedentary day (group 2; n=10). Each subject will be studied twice, once after taking oral GLN, once after placebo, in separate clinical research center (CRC) admissions a few weeks apart, in random order.

Should the investigators hypothesis prove to be true, it would warrant long term studies to determine whether sustained dietary GLN supplementation can decrease insulin requirements and ultimately improve diabetes control in teenagers with T1DM, If successful, this approach could potentially have a significant positive impact in terms of adolescent health.


Condition Intervention
Type I Diabetes Mellitus
Dietary Supplement: Glutamine
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Dietary Amino Acids and Insulin Sensitivity in Children With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Nemours Children's Clinic:

Primary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    To determine whether dietary amino acids such as glutamine supplementation, enhance either peripheral or hepatic insulin sensitivity in adolescents with type 1 diabetes mellitus (T1D)


Secondary Outcome Measures:
  • Glutamine mechanism of action [ Time Frame: 1 month ] [ Designated as safety issue: No ]

    To determine whether glutamine supplementation

    1. enhances citrulline, arginine, and nitric oxide (NO) production;
    2. increases glutathione (GSH) availability; and
    3. increases glucagon-like peptide 1 (GLP-1) secretion.


Estimated Enrollment: 20
Study Start Date: October 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glutamine Dietary Supplement: Glutamine
Participants will keep a diary of food intake and activity as well as wear an accelerometer (to measure overall movement) for 2-3 days prior to the admission. Subject will come to the Clinical Research Center for approximately 24 hours. They will receive a drink containing Glutamine (0.25 g/kg/dose). Afterwards they will have an afternoon exercise session consisting of 15-min bouts of exercise, interspersed with 5-min rest periods in between for a total of 75min. Blood glucose will be checked during rest intervals. They will be served a controlled dinner. Before bedtime another dose of the same drink will be given. Overnight blood glucose will be monitored closely. In the morning, another dose of the same drink will be given. Subjects will have two isotope infusions (non-radioactive) running concomitantly and a hyperinsulinemic-euglycemic clamp will be performed. Afterwards lunch will be served and subject discharged home.
Placebo Comparator: Placebo Dietary Supplement: Placebo
Participants will keep a diary of food intake and activity as well as wear an accelerometer (to measure overall movement) for 2-3 days prior to the admission. Subject will come to the Clinical Research Center for approximately 24 hours. They will receive a PLACEBO drink. Afterwards they will have an afternoon exercise session consisting of 15-min bouts of exercise, interspersed with 5-min rest periods in between for a total of 75min. Blood glucose will be checked during rest intervals. They will be served a controlled dinner. Before bedtime another dose of the same drink will be given. Overnight blood glucose will be monitored closely. In the morning, another dose of the same drink will be given. Subjects will have two isotope infusions (non-radioactive) running concomitantly and a hyperinsulinemic-euglycemic clamp will be performed. Afterwards lunch will be served and subject discharged home.

  Eligibility

Ages Eligible for Study:   13 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type I diabetes diagnosed for > 12 months.
  • Minimal weight of 40 kg
  • Tanner stage IV or beyond
  • All insulin programs, including intermediate/short acting insulins, Lantus/Detemir and short acting insulin or insulin pump therapy.
  • HbA1C between 7.5 and 10%
  • BMI between 10th to 85th percentile
  • Patients on stable thyroid replacement therapy will be allowed to participate.

Exclusion Criteria:

  • Celiac disease (any patient with history of positive serology or consuming a gluten-free diet)
  • Cystic Fibrosis
  • Chronic steroid therapy
  • Chronic medications that may interfere with glucose metabolism or liver function
  • History of mental retardation
  • Presence of diabetic complications
  • Positive pregnancy test
  • Presence of significant anemia (Hb<11 g/dL)
  • Presence of intercurrent infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01467063

Locations
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Sponsors and Collaborators
Nemours Children's Clinic
Thrasher Research Fund
Investigators
Principal Investigator: Dominique Darmaun, MD, PhD Nemours Children's Clinic
  More Information

Publications:
Responsible Party: Dominique Darmaun, Prinicipal Investigator, Nemours Children's Clinic
ClinicalTrials.gov Identifier: NCT01467063     History of Changes
Other Study ID Numbers: IRC# 11-29
Study First Received: November 2, 2011
Last Updated: May 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Nemours Children's Clinic:
Type I Diabetes
Insulin Resistance
Glutamine
Amino Acids
Glucagon like peptide 1
Glutathione
Citrulline
Arginine
Nitric Oxide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014