Diabetes Mellitus, Type 1Phase 2PHROGNCT04432090
GPR119 Agonist for Hypoglycemia in Type 1 Diabetes
A Phase 2 study testing Study Medication (MBX-2982) and No medication for this group in people with Diabetes Mellitus, Type 1, run by AdventHealth Translational Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Study Medication (MBX-2982) and No medication for this group
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2021to 12 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Type 1 diabetes cohort:
- Age 20-60 years
- Diagnosis of T1DM according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival
- Diabetes diagnosis performed more than 5 years before enrollment
- Fasting C-peptide levels < 0.7 ng/mL with a concurrent plasma glucose concentration > 90 mg/dL (Labs may need to be repeated if the Plasma glucose is < 90 mg/dL)
- For female participants: must be > 6 months post-partum and not lactating and 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.
Show all 13Show fewer
- Healthy subject cohort:
- Age 20-60 years
- General good health
- Creatinine clearance >80 mL/min based on CKD-EPI equation
- Fasting blood glucose (FBG) >70 mg/dL and <100 mg/dL
- No history of diabetes
- For female participants: must be > 6 months post-partum and not lactating and agrees not to become pregnant during the study
Who cannot join
- BMI >35 kg/m2 and <18.5 kg/m2 for females and BMI >35 kg/m2 and <20 kg/m2 for males.
- Increase or decrease body weight greater than 3kg in the 3 months before enrollment.
- Evidence by history, ECG or exams of clinically significant cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on ECG, presence of cardiac pacemaker, implanted cardiac defibrillator)
- Evidence of autonomic neuropathy
- Liver disease (AST or ALT >2.5 times the upper limit of normal)
- Kidney disease (creatinine >1.6 mg/dl or estimated GFR <60 ml/min).
Show all 42Show fewer
- 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.
- Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)
- Thyroid dysfunction (suppressed TSH, elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic)
- Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic) or treatment with more than 2 antihypertensive medications.
- Current use of beta-adrenergic blocking agents or their use was stopped less than one month before recruitment
- History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)
- History of organ transplant
- History of HIV, active Hepatitis B or C, or Tuberculosis
- Pregnancy, lactation or 6 months postpartum from the scheduled date of screening lab collection
- 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). Male participants: he or he and his partner unwilling to use an approved method of contraception with ≥99% effectiveness when used consistently and correctly
- History of Major Depression in the last 5 years
- History of an eating disorder
- History of bariatric surgery
- History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years
- Self-report of marijuana use ≥3 days/week in any form
- Psychiatric disease prohibiting adherence to study protocol
- Current use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs
- Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone or estrogen replacement therapy). Hormone based contraception is acceptable.
- Use of any medications known to influence glucose, fat and/or energy metabolism (e.g., growth hormone therapy, glucocorticoids [steroids], prescribed medications for weight loss, etc.). Patients on medications with acute effects on glucose metabolism used for other indications (certain antidepressants, ADHD and antiepileptic medications) may be enrolled if they have been on chronic, stable doses (≥6 months)
- Uncontrolled seizure disorder
- Current night shift worker
- 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
- Unwilling and/or unable to follow and comply with scheduled visits and protocol requirements
- Additional exclusion Criteria for the type 1 diabetes cohort:
- HbA1c >9%
- Insulin dose less than 0.3 U/kg or low carbohydrate diet
- History of T2DM or any form of diabetes other than T1DM
- Hypoglycemia unawareness as assessed using the GOLD score
- 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.
- Two or more episodes of severe hypoglycemia (Hypoglycemia requiring help from a third party) per month in the past six months
- One or more DKA episodes in the past 3 months
- QTcF >450 msec for males and >470 msec for females
- Using non-insulin agents to control blood glucose levels
- History or evidence of moderate or severe end-organ diabetic complications of retinopathy, nephropathy or neuropathy. Proliferative diabetic retinopathy. Non-proliferative retinopathy and microalbuminuria will be allowed.
- Additional exclusion Criteria for the healthy cohort:
- 1. Insulin treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
AdventHealth Translational Research Institute
Orlando, Florida, 32804
About this study
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
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.
Read the detailed description
This is a placebo-controlled, double-blinded, within-subject, cross-over phase 2a study. In randomized order, (Latin square, randomly assigned to placebo-active and active-placebo periods) and in a double-blinded manner, the participants with T1D received 14 days of daily dosing with MBX-2982 (or placebo), taken at the same time each day after breakfast. The last dose of treatment/placebo was given when the glucose tracer infusion for the euglycemic/hypoglycemic-glucose clamp started. Participants with T1D underwent two euglycemic-hypoglycemic clamps (induction of controlled hypoglycemia by an insulin infusion), using a within-subject cross-over design, with the two clamps separated by approximately four weeks, that is, two weeks of drug washout followed by two weeks of treatment with the alternative therapy. Glucagon, hepatic glucose production and other counter-regulatory hormonal responses were assessed during hypoglycemia. After completion of the first clamp study, participants did not receive any study medication for two weeks (washout phase) and then begin 14 days of the other arm (placebo or MBX-2982) in a double-blinded manner, followed by a repeat euglycemic-hypoglycemic clamp study. During treatment on each arm and during wash out phase, a blinded CGM was used to assess daily and nocturnal patterns of glycemia. On the day preceding a clamp study, while admitted to the research unit, a standardized meal test was used to assess fasting and postprandial glucagon, GLP-1 and GIP secretion. A healthy normal volunteer cohort with no diabetes was enrolled in the study for 14 days for comparison of normal responses to insulin induced hypoglycemia.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Placebo, Study Medication (MBX-2982), No medication for this group
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called 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)
Study Medication (MBX-2982)Drug
Also called 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)
No medication for this groupOther
This group will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
| Study group | Role | What they receive |
|---|---|---|
| MBX-2982 first then placebo- Volunteers with Type 1 diabetes | Experimental | Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that contains the study medication (MBX-2982). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that does not contain the medication (placebo). Receives: Drug: Placebo; Drug: Study Medication (MBX-2982) |
| Healthy Volunteers | Active comparator | 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. Receives: Other: No medication for this group |
| Placebo first then MBX-2982- Volunteers with Type 1 diabetes | Experimental | Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that does not contain the medication (placebo). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that contains the study medication (MBX-2982). Receives: Drug: Placebo; Drug: Study Medication (MBX-2982) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Glucagon Concentration During Hypoglycemia
Maximal glucagon concentration during insulin induced hypoglycemia. This was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic-hypoglycemic clamp study.
Measured: Day 14, Day 42
Total Area Under the Curve (AUC) for Glucagon During Hypoglycemia.
This outcome was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic hypoglycemic clamp study. Total area under the curve (AUC) for glucagon was measured during the time points of 120 minutes to 140 minutes of the clamp.
Measured: Day 14, Day 42
Incremental AUC for Glucagon During Hypoglycemia (Above Baseline Levels During Euglycemia)
This is the difference between the AUC during the hypoglycemic steady state (time points 120 - 140 mins of clamp) and the baseline glucagon levels during euglycemic steady state (timepoints 60 min - 80 mins of the clamp)
Measured: Day 14, Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start21 Apr 2021
- Primary completion12 Aug 2023
- Study completion12 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- AdventHealth Translational Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Pratley, MD, Principal investigator, Study Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04432090
- Sponsor's protocol ID
- 1552172
- Acronym
- PHROG
- Status last verified
- Oct 2024
- First submitted
- 9 Jun 2020
- Last updated
- 17 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ekberg JH, Hauge M, Kristensen LV, Madsen AN, Engelstoft MS, Husted AS, Sichlau R, Egerod KL, Timshel P, Kowalski TJ, Gribble FM, Reiman F, Hansen HS, Howard AD, Holst B, Schwartz TW. GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40). Endocrinology. 2016 Dec;157(12):4561-4569. doi: 10.1210/en.2016-1334. Epub 2016 Oct 25.
PubMed 27779915Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology. 2011 Feb;152(2):374-83. doi: 10.1210/en.2010-1047. Epub 2010 Nov 10.
PubMed 21068156Lauffer LM, Iakoubov R, Brubaker PL. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. 2009 May;58(5):1058-66. doi: 10.2337/db08-1237. Epub 2009 Feb 10.
PubMed 19208912Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood HB, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes. 2018 Jul;67(7):1401-1413. doi: 10.2337/db18-0031. Epub 2018 Apr 18.
PubMed 29669745Segerstolpe A, Palasantza A, Eliasson P, Andersson EM, Andreasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, Smith DM, Kasper M, Ammala C, Sandberg R. Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes. Cell Metab. 2016 Oct 11;24(4):593-607. doi: 10.1016/j.cmet.2016.08.020. Epub 2016 Sep 22.
PubMed 27667667Bolli G, Calabrese G, De Feo P, Compagnucci P, Zega G, Angeletti G, Cartechini MG, Santeusanio F, Brunetti P. Lack of glucagon response in glucose counter-regulation in type 1 (insulin-dependent) diabetics: absence of recovery after prolonged optimal insulin therapy. Diabetologia. 1982 Feb;22(2):100-5. doi: 10.1007/BF00254837.
PubMed 7037510Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973 Oct 12;182(4108):171-3. doi: 10.1126/science.182.4108.171.
PubMed 4581053Gerich JE. Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus. Diabetes. 1988 Dec;37(12):1608-17. doi: 10.2337/diab.37.12.1608.
PubMed 3056759Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997 Feb;46(2):271-86.
PubMed 9000705Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.1038/nrendo.2014.170. Epub 2014 Oct 7.
PubMed 25287289UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007 Jun;50(6):1140-7. doi: 10.1007/s00125-007-0599-y. Epub 2007 Apr 6.
PubMed 17415551Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013 Jul 25;369(4):362-72. doi: 10.1056/NEJMra1215228. No abstract available.
PubMed 23883381Rizza RA, Cryer PE, Gerich JE. Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia. J Clin Invest. 1979 Jul;64(1):62-71. doi: 10.1172/JCI109464.
PubMed 36413Yue JT, Burdett E, Coy DH, Giacca A, Efendic S, Vranic M. Somatostatin receptor type 2 antagonism improves glucagon and corticosterone counterregulatory responses to hypoglycemia in streptozotocin-induced diabetic rats. Diabetes. 2012 Jan;61(1):197-207. doi: 10.2337/db11-0690. Epub 2011 Nov 21.
PubMed 22106159Szewczyk JW, Acton J, Adams AD, Chicchi G, Freeman S, Howard AD, Huang Y, Li C, Meinke PT, Mosely R, Murphy E, Samuel R, Santini C, Yang M, Zhang Y, Zhao K, Wood HB. Design of potent and selective GPR119 agonists for type II diabetes. Bioorg Med Chem Lett. 2011 May 1;21(9):2665-9. doi: 10.1016/j.bmcl.2010.12.086. Epub 2010 Dec 22.
PubMed 21273063
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04432090
- Acronym / sponsor ID
- PHROG / 1552172
- Conditions
- Diabetes Mellitus, Type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- AdventHealth Translational Research InstituteUniversity, hospital or other
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 12 Aug 2023 (actual)
- Study completion
- 12 Aug 2023 (actual)
- First posted
- 16 Jun 2020 (actual)
- Results
- Posted 17 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a placebo-controlled, double-blinded, within-subject, cross-over phase 2a study. In randomized order, (Latin square, randomly assigned to placebo-active and active-placebo periods) and in a double-blinded manner, the participants with T1D received 14 days of daily dosing with MBX-2982 (or placebo), taken at the same time each day after breakfast. The last dose of treatment/placebo was given when the glucose tracer infusion for the euglycemic/hypoglycemic-glucose clamp started. Participants with T1D underwent two euglycemic-hypoglycemic clamps (induction of controlled hypoglycemia by an insulin infusion), using a within-subject cross-over design, with the two clamps separated by approximately four weeks, that is, two weeks of drug washout followed by two weeks of treatment with the alternative therapy. Glucagon, hepatic glucose production and other counter-regulatory hormonal responses were assessed during hypoglycemia. After completion of the first clamp study, participants did not receive any study medication for two weeks (washout phase) and then begin 14 days of the other arm (placebo or MBX-2982) in a double-blinded manner, followed by a repeat euglycemic-hypoglycemic clamp study. During treatment on each arm and during wash out phase, a blinded CGM was used to assess daily and nocturnal patterns of glycemia. On the day preceding a clamp study, while admitted to the research unit, a standardized meal test was used to assess fasting and postprandial glucagon, GLP-1 and GIP secretion. A healthy normal volunteer cohort with no diabetes was enrolled in the study for 14 days for comparison of normal responses to insulin induced hypoglycemia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MBX-2982 first then placebo- Volunteers with Type 1 diabetes | Experimental | Drug: Placebo, Drug: Study Medication (MBX-2982)Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that contains the study medication (MBX-2982). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that does not contain the medication (placebo). |
| Healthy Volunteers | Active comparator | Other: No medication for this groupThis 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. |
| Placebo first then MBX-2982- Volunteers with Type 1 diabetes | Experimental | Drug: Placebo, Drug: Study Medication (MBX-2982)Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that does not contain the medication (placebo). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that contains the study medication (MBX-2982). |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Age 20-60 years
- Diagnosis of T1DM according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival
- Diabetes diagnosis performed more than 5 years before enrollment
- Fasting C-peptide levels < 0.7 ng/mL with a concurrent plasma glucose concentration > 90 mg/dL (Labs may need to be repeated if the Plasma glucose is < 90 mg/dL)
- For female participants: must be > 6 months post-partum and not lactating and 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.
Key exclusion criteria (42 listed)
- BMI >35 kg/m2 and <18.5 kg/m2 for females and BMI >35 kg/m2 and <20 kg/m2 for males.
- Increase or decrease body weight greater than 3kg in the 3 months before enrollment.
- Evidence by history, ECG or exams of clinically significant cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on ECG, presence of cardiac pacemaker, implanted cardiac defibrillator)
- Evidence of autonomic neuropathy
- Liver disease (AST or ALT >2.5 times the upper limit of normal)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: MBX-2982Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo) | Drug | MBX-2982 first then placebo- Volunteers with Type 1 diabetes, Placebo first then MBX-2982- Volunteers with Type 1 diabetes |
| Study Medication (MBX-2982)Also: MBX-2982Each group will receive either a pill that contains the study medication (MBX-2982) or a pill that does not contain the medication (placebo) | Drug | MBX-2982 first then placebo- Volunteers with Type 1 diabetes, Placebo first then MBX-2982- Volunteers with Type 1 diabetes |
| No medication for this groupThis group will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes. | Other | Healthy Volunteers |
Primary outcome
Maximal Glucagon Concentration During Hypoglycemia
Time frame: Day 14, Day 42
Maximal glucagon concentration during insulin induced hypoglycemia. This was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic-hypoglycemic clamp study.
Total Area Under the Curve (AUC) for Glucagon During Hypoglycemia.
Time frame: Day 14, Day 42
This outcome was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic hypoglycemic clamp study. Total area under the curve (AUC) for glucagon was measured during the time points of 120 minutes to 140 minutes of the clamp.
Incremental AUC for Glucagon During Hypoglycemia (Above Baseline Levels During Euglycemia)
Time frame: Day 14, Day 42
This is the difference between the AUC during the hypoglycemic steady state (time points 120 - 140 mins of clamp) and the baseline glucagon levels during euglycemic steady state (timepoints 60 min - 80 mins of the clamp)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27779915Ekberg JH, Hauge M, Kristensen LV, Madsen AN, Engelstoft MS, Husted AS, Sichlau R, Egerod KL, Timshel P, Kowalski TJ, Gribble FM, Reiman F, Hansen HS, Howard AD, Holst B, Schwartz TW. GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40). Endocrinology. 2016 Dec;157(12):4561-4569. doi: 10.1210/en.2016-1334. Epub 2016 Oct 25.
- Background: PubMed 21068156Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology. 2011 Feb;152(2):374-83. doi: 10.1210/en.2010-1047. Epub 2010 Nov 10.
- Background: PubMed 19208912Lauffer LM, Iakoubov R, Brubaker PL. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. 2009 May;58(5):1058-66. doi: 10.2337/db08-1237. Epub 2009 Feb 10.
- Background: PubMed 29669745Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood HB, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes. 2018 Jul;67(7):1401-1413. doi: 10.2337/db18-0031. Epub 2018 Apr 18.
- Background: PubMed 27667667Segerstolpe A, Palasantza A, Eliasson P, Andersson EM, Andreasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, Smith DM, Kasper M, Ammala C, Sandberg R. Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes. Cell Metab. 2016 Oct 11;24(4):593-607. doi: 10.1016/j.cmet.2016.08.020. Epub 2016 Sep 22.
- Background: PubMed 7037510Bolli G, Calabrese G, De Feo P, Compagnucci P, Zega G, Angeletti G, Cartechini MG, Santeusanio F, Brunetti P. Lack of glucagon response in glucose counter-regulation in type 1 (insulin-dependent) diabetics: absence of recovery after prolonged optimal insulin therapy. Diabetologia. 1982 Feb;22(2):100-5. doi: 10.1007/BF00254837.
- Background: PubMed 4581053Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973 Oct 12;182(4108):171-3. doi: 10.1126/science.182.4108.171.
- Background: PubMed 3056759Gerich JE. Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus. Diabetes. 1988 Dec;37(12):1608-17. doi: 10.2337/diab.37.12.1608.
- Background: PubMed 9000705Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997 Feb;46(2):271-86.
- Background: PubMed 25287289Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014 Dec;10(12):711-22. doi: 10.1038/nrendo.2014.170. Epub 2014 Oct 7.
- Background: PubMed 17415551UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007 Jun;50(6):1140-7. doi: 10.1007/s00125-007-0599-y. Epub 2007 Apr 6.
- Background: PubMed 23883381Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013 Jul 25;369(4):362-72. doi: 10.1056/NEJMra1215228. No abstract available.
- Individual participant dataSharing planned: No
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type1diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Pratley, MD principal investigator
Study Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Study Medication (MBX-2982) and No medication for this group in people with Diabetes Mellitus, Type 1, run by AdventHealth Translational Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Glucagon Concentration During Hypoglycemia (time frame: Day 14, Day 42). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04432090, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2024.