Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04432090
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Translational Research Institute for Metabolism and Diabetes, Florida

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Placebo Drug: Study Medication (MBX-2982) Other: No medication for this group Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: 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
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021


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)




Primary Outcome Measures :
  1. Maximal glucagon concentration during hypoglycemia [ Time Frame: Day 14, Day 28, 6 hours ]
  2. Total area under the curve (AUC) for glucagon during hypoglycemia. [ Time Frame: Day 14, Day 28, 6 hours ]
  3. Incremental AUC for glucagon during hypoglycemia (above baseline levels during euglycemia) [ Time Frame: Day 14, Day 28, 6 hours ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04432090


Contacts
Layout table for location contacts
Contact: Recruitment Department 407-303-7100 Fh.tri.recruitment@adventhealth.com

Locations
Layout table for location information
United States, Florida
AdventHealth Translational Research Institute Recruiting
Orlando, Florida, United States, 32804
Contact: Recruitment Department    407-303-7100    Fh.tri.recruitment@adventhealth.com   
Sponsors and Collaborators
Translational Research Institute for Metabolism and Diabetes, Florida
Investigators
Layout table for investigator information
Principal Investigator: Richard Pratley, MD Study Principal Investigator
Publications:

Layout table for additonal information
Responsible Party: Translational Research Institute for Metabolism and Diabetes, Florida
ClinicalTrials.gov Identifier: NCT04432090    
Other Study ID Numbers: 1552172
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases