A single-center pilot study to establish a novel hypoglycemic clamp procedure to assess the time to spontaneous recovery from hypoglycemia in people with and without diabetes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Graz

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Hormonal diseases [C19]

Trial duration

2 Jul 2025 → 7 Nov 2025

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Eli Lilly Regional Operations Ges.m.b.H

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To describe the relationship in the insulin dose required to lower plasma glucose (PG) from 90 – 70 mg/dL versus lowering PG from 70 – 48 mg/dL

Secondary objectives 3

1. To describe the relationship in the insulin dose required to induce hypoglycemia in people with diabetes compared with people without diabetes
2. To describe the amount of insulin needed for hypoglycemia induction
3. To assess feasibility of the hypoglycemic clamp procedure

Conditions and MedDRA coding

Type 2 Diabetes Mellitus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Inclusion Criteria for Participants with Diabetes: 1. Participant must be 18 to 64 years of age, both inclusive, at the time of signing the informed consent. 2. Have been diagnosed with T2D for at least 6 months prior to screening. 3. Treated with diet and exercise and stable treatment with metformin with or without allowed OAM or GLP-1 receptor agonists, 3 months prior to screening (allowed OAMs include DPP-IV inhibitors, SGLT2 inhibitors, glinides, or sulfonylureas). 4. Have a HbA1c value of ≤9.5% at screening (Visit 1). 5. Have venous access sufficient to allow for blood sampling as per the protocol. 6. Have clinical laboratory test results within normal reference range for the population or results with acceptable deviations that are judged to be not clinically significant by the Investigator. 7. Have a body mass index (BMI) within the range 25.0 kg/m2 and 45.0 kg/m2 (both inclusive). 8. Have had a stable body weight that is less than 5% change in body weight for more than 3 months prior to screening (Visit 1). 9. Agree not to initiate an intensive diet or exercise program during the study with the intent of reducing body weight other than lifestyle and dietary measures for diabetes treatment. 10. Women of childbearing potential (WOCBP) must use highly effective contraceptive methods, stable at least 2 months prior to the screening. 11. Are capable of giving signed informed consent as described in Section 10.1.2 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 12. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
2. Inclusion Criteria for Participants without Diabetes: 1. Participant must be 18 to 64 years of age, both inclusive, at the time of signing the informed consent. 2. Considered to be healthy based on medical history, physical examination, results of vital signs and ECG. 3. Have venous access sufficient to allow for blood sampling as per the protocol. 4. Have clinical laboratory test results within normal reference range for the population or results with acceptable deviations that are judged to be not clinically significant by the Investigator. 5. Have a body mass index (BMI) within the range 25.0 kg/m2 and 29.9 kg/m2 (both inclusive). 6. Have had a stable body weight that is less than 5% change in body weight for more than 3 months prior to screening (Visit 1). 7. Agree not to initiate an intensive diet or exercise program during the study with the intent of reducing body weight other than lifestyle and dietary measures for diabetes treatment. 8. WOCBP must use highly effective contraceptive methods, stable at least 2 months prior to the screening. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For the contraception requirements of this protocol. For methods of contraception see Section 10.4. 9. Are capable of giving signed informed consent as described in Section 10.1.2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 10. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion criteria 8

1. Exclusion Criteria for Participants with Diabetes - Medical Conditions: 1. Have type 1 diabetes mellitus. 2. Have known allergies to insulin aspart. 3. Have had an episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before screening or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms. 4. Do not have enough ability to communicate an understanding of hypoglycemic symptoms and the appropriate treatment of hypoglycemia in the opinion of the Investigator. 5. Have had an episode of ketoacidosis or hyperosmolar state/coma requiring hospitalization within the 6 months prior to screening (Visit 1). 6. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator. 7. Have impaired renal estimated glomerular filtration rate <60 mL/min/1.73 m2 calculated by Chronic Kidney Disease-Epidemiology. 8. Show evidence of possible chronic or active hepatitis B, including hepatitis B core antibody and/or hepatitis B surface antigen positivity. 9. Have a positive HCV antibody test. Participants with a positive HCV antibody test at screening can be included only if a confirmatory HCV RNA test is negative. 10. Have evidence of HIV infection and/or positive HIV antibodies. 11. Have a history of • acute myocardial infarction, • peripheral artery disease, • ischemic heart disease, • congestive heart failure, New York Heart Association class III or IV, • cerebrovascular accident (stroke [including transient ischemic attack]), • coronary artery revascularization, • hospitalization for unstable angina, and/or • hospitalization due to congestive heart failure. 12. Have a history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalemia, family history of Long QT Syndrome). 13. Have a 12-lead ECG abnormality at screening that, in the opinion of the Investigator, increases the risks associated with participating in the study or may confound ECG data analysis. 14. Have the following sustained measurements at screening for at least 3 months: systolic blood pressure of greater than 160 mm Hg, diastolic blood pressure of greater than 100 mm Hg, or sitting pulse rate of less than 50 bpm or greater than 100 bpm. This exclusion criterion also pertains to participants being on antihypertensives. 15. Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for <5 years prior to screening (Visit 1). Exceptions: • Basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; • Cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline; or • In situ prostate cancer. 16. Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointenstinal, endocrine, hematological, neurological, or mental health disorders constituting a risk when undergoing hypoglycemic clamp; or of interfering with the interpretation of data, as judged by the Investigator. 17. Have had a blood donation of 500 mL or more in the last 3 months or any blood donation within the last month prior to screening (Visit 1). 18. Have a history of significant atopy (severe or multiple allergic manifestations), or anaphylactic reaction.
2. Exclusion Criteria for Participants with Diabetes - Prior or Concomitant Therapy: 19. Have taken any glucose-lowering medications other than metformin, DPP-IV inhibitors, sulfonylureas, glinides, or SGLT2 inhibitors or GLP-1 receptor agonists any time within the 3 months prior to screening. • Short term use of insulin (<14 days) for treatment of acute conditions is allowed in the 3-month period prior to screening. 20. Treated with any medication known to interfere with glucose metabolism, i.e. non-selective beta-blockers, systemic glucocorticoid therapy (excluding topical, intraarticular or inhaled preparations not reaching circulation), monoamine oxidase (MAO) inhibitors within 30 days or 5 half-lifes (whichever is longer) before screening. Stable therapy with hormonal contraceptives (2 months) is allowed.
3. Exclusion Criteria for Participants with Diabetes - Substance Abuse: 21. Having a history of alcohol abuse within 1 year prior to screening, or positive alcohol breath test at screening. 22. Smoke more than 10 cigarettes, or cigarette equivalent (as determined by Investigator), per day or are unable to abide by the study site’s tobacco and nicotine containing product restrictions. 23. History of drug abuse or positive result on urine drug test for drugs of abuse at screening. Have evidence of current or history of any substance use disorder(s) of any severity as defined by the DSM-V in the opinion of the Investigator, excepting disorders of nicotine or caffeine use. 24. Are unwilling to comply with the lifestyle and dietary restrictions required for this study.
4. Exclusion Criteria for Participants with Diabetes - Others: 25. Women who are lactating, pregnant or intend to become pregnant or to breastfeed during the study. 26. Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. 27. Are study site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
5. Exclusion Criteria for Participants without Diabetes - Medical Conditions: 1. Have impaired renal estimated glomerular filtration rate <60 mL/min/1.73 m2 calculated by Chronic Kidney Disease-Epidemiology. 2. Show evidence of possible chronic or active hepatitis B, including hepatitis B core antibody and/or hepatitis B surface antigen positivity. 3. Have a positive HCV antibody test. Participants with a positive HCV antibody test at screening can be included only if a confirmatory HCV RNA test is negative. 4. Have evidence of HIV infection and/or positive HIV antibodies. 5. Have a history of • acute myocardial infarction, • peripheral artery disease, • ischemic heart disease, • congestive heart failure, New York Heart Association class III or IV, • cerebrovascular accident (stroke [including transient ischemic attack]), • coronary artery revascularization, • hospitalization for unstable angina, and/or • hospitalization due to congestive heart failure. 6. Have a history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalemia, family history of Long QT Syndrome). 7. Have a 12-lead ECG abnormality at screening that, in the opinion of the Investigator, increases the risks associated with participating in the study or may confound ECG data analysis. 8. Supine blood pressure at screening outside the range of 90 – 140 mmHg for systolic or 50 – 90 mmHg for diastolic (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the participant can be included in the study). 9. Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for <5 years prior to screening (Visit 1). Exceptions: • Basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; • Cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline; or • In situ prostate cancer. 10. Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointenstinal, endocrine, hematological, neurological, or mental health disorders constituting a risk when undergoing hypoglycemic clamp; or of interfering with the interpretation of data, as judged by the Investigator. 11. Have had a blood donation of 500 mL or more in the last 3 months or any blood donation within the last month prior to screening (Visit 1). 12. Have a history of significant atopy (severe or multiple allergic manifestations), or anaphylactic reaction.
6. Exclusion Criteria for Participants without Diabetes - Prior or Concomitant Therapy: 13. Treated with any medication known to interfere with glucose metabolism, i.e. non-selective beta-blockers, systemic glucocorticoid therapy (excluding topical, intraarticular or inhaled preparations not reaching circulation), monoamine oxidase (MAO) inhibitors within 30 days or 5 half-lifes (whichever is longer) before screening. Stable therapy with hormonal contraceptives (2 months) is allowed.
7. Exclusion Criteria for Participants without Diabetes - Substance Abuse: 14. Having a history of alcohol abuse within 1 year prior to screening, or positive alcohol breath test at screening. 15. Smoke more than 10 cigarettes, or cigarette equivalent (as determined by Investigator), per day or are unable to abide by the study site’s tobacco and nicotine containing product restrictions. 16. History of drug abuse or positive result on urine drug test for drugs of abuse at screening. Have evidence of current or history of any substance use disorder(s) of any severity as defined by the DSM-V in the opinion of the Investigator, excepting disorders of nicotine or caffeine use. 17. Are unwilling to comply with the lifestyle and dietary restrictions required for this study.
8. Exclusion Criteria for Participants without Diabetes - Others: 18. Women who are lactating, pregnant or intend to become pregnant or to breastfeed during the study. 19. Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. 20. Are study site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Ratio of insulin rates (mU/kg/min) required to lower PG from 90 – 70 mg/dL within 90 min (±30 min) and insulin rates required to lower PG from 70 – 48 mg/dL within 90 min (±30 min)

Secondary endpoints 9

1. Comparison of the ratio of insulin rates derived in participants with diabetes versus the ratio of insulin rates derived in participants without diabetes
2. Comparison of the total insulin amount (mU/kg) required to achieve nadir (PG 48 mg/dL [2.7 mmol/L]) at the first clamp visit versus at the second clamp visit
3. Comparison of the total insulin amount (mU/kg) required to achieve nadir (PG 48 mg/dL [2.7 mmol/L]) in participants with versus participants without diabetes
4. Number of participants who achieved spontaneous recovery from hypoglycemia
5. Number of participants who did not reach nadir (PG 48 mg/dL [2.7 mmol/L])
6. Number of participants who did not spontaneously recovered after reaching nadir
7. Time to spontaneous recovery from hypoglycemia
8. Glucose i.v. (mg/kg) administered within the first 30 minutes after reaching nadir (PG 48 mg/dL [2.7 mmol/L])
9. Rescue glucose i.v. (mg/kg) administered from 31 – 60 minutes after reaching nadir (PG 48 mg/dL [2.7 mmol/L])

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Graz

Sponsor organisation

Medical University Of Graz

Address

Neue Stiftingtalstrasse 6

City

Graz

Postcode

8010

Country

Austria

Scientific contact point

Organisation

Medical University Of Graz

Contact name

Dr. Eva Svehlikova

Public contact point

Organisation

Medical University Of Graz

Contact name

Prof. Thomas Pieber

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications