Glucagon-like Peptide-1 in Type 1 Diabetes

Reducing Hypoglycemic, Pro-coagulant and Pro-atherothrombotic Responses and Preventing Hypoglycemia Associated Autonomic Failure in Type 1 DM. The Effects of Glucagon-like Peptide-1

The hypotheses to be tested in this application is: GLP-1 will acutely protect arterial endothelial function and reduce pro-atherothrombotic and pro-coagulant effects of repeated hypoglycemia in T1DM.

Study Overview

• Status: Recruiting
• Conditions: Type1 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebos; Drug: Glucagon-like peptide-1

Detailed Description

The naturally occurring hormone GLP-1 when co-administered during hypoglycemia (low blood sugar) in non-diabetic individuals can reduce the deleterious effects of hypoglycemia on the vasculature. We have shown that IV infusion of GLP-1 during a single moderate episode of hypoglycemia can preserve endothelial function and protect the vasculature from pro-coagulant and pro-inflammatory effects in healthy individuals.

It is unknown whether GLP-1 could protect the vasculature during episodes of repeated hypoglycemia and whether GLP-1 would have protective effects in T1DM individuals.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Stephen N Davis, MBBS
• Study Contact Backup: Name: Maka Siamashvili, MD; Phone Number: 410-706-5623; Email: msiamashvili@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland
      • Contact: Maka Siamashvili, MD; Phone Number: 615-715-9494; Email: msiamashvili@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 40 (20 males, 20 females) individuals with type 1 diabetes aged 18-50 yr.
• HbA1c < 11.0%
• Body mass index < 40kg • m-2
• No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc)

Exclusion Criteria:

• Subjects unable to give voluntary informed consent
• Pregnancy
• Subjects on anticoagulant drugs, anemic or with known bleeding diatheses
• Subjects taking any of the following medications will be excluded: non-selective beta blockers,
• sedative-hypnotics, anticonvulsants, antiparkinsonian drugs, antipsychotics, antidepressants,
• mood stabilizers, CNS stimulants, opioids, hallucinogens
• Subjects unwillingness or inability to comply with approved contraception measures
• Subjects with a history of severe uncontrolled hypertension (i.e., blood pressure greater than 160/100), heart disease, cerebrovascular incidents
• Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmias, ischemic tachycardia, S-T segment deviations, etc.) from history or from cardiac stress testing in subjects ≥ 40 years old.
• Pneumonia
• Hepatic failure /jaundice
• Abnormal results following screening tests and physical examination that are clinically significant
• Acute cerebrovascular/ neurological deficit
• Fever greater than 38.0 C
• Screening Laboratory Tests Exclusion Criteria
• Hematocrit lower than 32
• WBC lower than 3 thou/ul or greater than 14 thou/ul
• Liver function tests: SGOT and SGPT greater than twice upper limit of normal range (i.e. > 80 U/L)
• TBil > 2 mg/dl
• Creatinine > 1.6 mg/dl
• Alkaline phosphatase > 150U/L
• Hepatic transaminase > 2x normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo 1; The participants will be randomized to placebo infusion.	Drug: Placebos; Infusion of normal saline solution that will mimic Glucagon-like peptide-1
Placebo Comparator: Placebo 2; The participants will be randomized to placebo infusion.	Drug: Placebos; Infusion of normal saline solution that will mimic Glucagon-like peptide-1
Experimental: GLP-1; The participants will be randomized to Glucagon-like peptide-1 infusion.	Drug: Glucagon-like peptide-1; Infusion of Glucagon-like peptide-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the level of catecholamines in plasma	3 years

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: HP-00090856

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No