Study of the Pharmacologic Action of a GPR119 Agonist on Glucagon Counter-regulation During Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus (PHROG)

February 5, 2024 updated by: AdventHealth Translational Research Institute

A Randomized, Placebo-controlled, Double-blinded Cross-over Study of the Pharmacologic Action of a GPR119 Agonist on Glucagon Counter-regulation During Insulin-induced Hypoglycemia in Type 1 Diabetes Mellitus

The purpose of this study is to test if a specific research medication could increase the response to low blood glucose in people with type 1 diabetes. The response of the body to low blood sugar will be measured in healthy people as a reference point.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32804
        • AdventHealth Translational Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Type 1 diabetes cohort

  1. Age >20 years
  2. Diagnosis of T1DM according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival
  3. Diabetes diagnosis performed more than 5 years before enrollment
  4. Fasting C-peptide levels < 0.7 ng/mL with a concurrent plasma glucose concentration > 90 mg/dL
  5. For female participants: agrees not to become pregnant during the study and for at least 2 weeks after the last dose of the study medication. For male participants: agrees not to donate sperm or not to get a woman pregnant during the study and for at least 2 weeks after the last dose of the study medication.

Healthy subject cohort

  1. Age >20 years
  2. General good health
  3. Creatinine clearance >80 mL/min based on MDRD equation
  4. Fasting blood glucose (FBG) >70 mg/dL and <100 mg/dL
  5. No history of diabetes

Exclusion Criteria:

  1. BMI >30 kg/m2 and <18.5 kg/m2
  2. No evidence by history, EKG or exams of symptomatic cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted cardiac defibrillator)
  3. Evidence of autonomic neuropathy
  4. Liver disease (AST or ALT >2.5 times the upper limit of normal)
  5. Kidney disease (creatinine >1.6 mg/dl or estimated GFR <60 ml/min).
  6. Dyslipidemia, including triglycerides >500 mg/dl, LDL >200 mg/dl or unstable hyperlipidemia. Treatment with a single lipid lowering agents is allowed if stable within the previous 3 months.
  7. Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)
  8. Thyroid dysfunction (suppressed thyroid stimulating hormone (TSH), elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic)
  9. Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic) or treatment with more than 2 antihypertensive medications
  10. History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable).
  11. History of organ transplant
  12. History of HIV, active Hepatitis B or C, or Tuberculosis
  13. Pregnancy, lactation or 6 months postpartum from the scheduled date of collection
  14. Females of childbearing potential (any female except those with tubal ligation, hysterectomy, or absence of menses >2 years) unwilling to use an approved method of contraception (one medically accepted method of contraception with ≥99% effectiveness when used consistently and correctly: implantable uterine device (IUD), hormonal contraception). Male participants: unwilling to use appropriate contraception (e.g. condoms) and/or their partner uses a medically accepted form of contraception during the study.
  15. History of Major Depression in the last 5 years
  16. History of an eating disorder
  17. History of bariatric surgery
  18. History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years
  19. Psychiatric disease prohibiting adherence to study protocol
  20. Use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs
  21. Current use of beta-adrenergic blocking agents or their use was stopped less than one month before recruitment
  22. Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone or estrogen replacement therapy)
  23. Use of any medications known to influence glucose, fat and/or energy metabolism within the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], prescribed medications for weight loss, etc.)
  24. Current night shift worker
  25. Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study visits Additional exclusion Criteria for type 1 diabetes cohort
  26. History of T2DM or any form of diabetes other than T1DM
  27. Hypoglycemia unawareness as assessed using the GOLD score
  28. Using a predictive low blood glucose suspend mode on an insulin pump or a hybrid closed loop algorithm for insulin delivery. For those applying these strategies for everyday management of blood glucose and willing to participate, the algorithm will be stopped at enrollment where possible.
  29. Two or more episode of severe hypoglycemia per month in the past six months.
  30. QTcF >450 ms for males and >470 ms for females
  31. Using non-insulin agents to control blood glucose levels.

  32. No evidence of moderate or severe end-organ diabetic complications of retinopathy, nephropathy or neuropathy. Non-proliferative retinopathy and microalbuminura will be allowed.

    Additional exclusion Criteria for the healthy cohort

  33. Insulin treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MBX-2982 first then placebo- Volunteers with Type 1 diabetes
This will be followed by a second study period in which they will be crossed over to the other treatment.
Drug: Placebo
Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)
Drug: Study Medication (MBX-2982)
Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)
Active Comparator: Healthy Volunteers
this group will not receive any medication. It will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
Other: No medication for this group
This group will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
Experimental: Placebo first then MBX-2982- Volunteers with Type 1 diabetes
Drug: Placebo
Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)
Drug: Study Medication (MBX-2982)
Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximal glucagon concentration during hypoglycemia
Time Frame: Day 14, Day 28, 6 hours
Day 14, Day 28, 6 hours
Total area under the curve (AUC) for glucagon during hypoglycemia.
Time Frame: Day 14, Day 28, 6 hours
Day 14, Day 28, 6 hours
Incremental AUC for glucagon during hypoglycemia (above baseline levels during euglycemia)
Time Frame: Day 14, Day 28, 6 hours
Day 14, Day 28, 6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth Translational Research Institute

Investigators

  • Principal Investigator: Richard Pratley, MD, Study Principal Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 21, 2021

Primary Completion (Actual)

November 11, 2022

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

June 9, 2020

First Submitted That Met QC Criteria

June 12, 2020

First Posted (Actual)

June 16, 2020

Study Record Updates

Last Update Posted (Estimated)

February 6, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1552172

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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