Study on Lixisenatide and Counterregulation to Hypoglycemia

NCT ID: NCT02020629

Last Updated: 2015-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2015-08-31

Brief Summary

In hypoglycemia, there is a counterregulation to restore glucose levels. An important part of this counterregulation is the release of the hormone glucagon. Since the GLP-1 receptor agonist lixisenatide has been shown to be associated with a low risk of hypoglycemia, this study examines whether lixisenatide affects the glucagon response to hypoglycemia.

Detailed Description

The study is a single-center, randomized, placebo-controlled study with a cross-over design and examines the glucagon response during a hyperinsulinemic hypoglycemic phase after a 6-week treatment with lixisenatide (or placebo) as add-on to basal insulin and metformin. The hypothesis of the study is that the glucagon counterregulation to hypoglycemia in patients treated with lixisenatide and basal insulin is not lower than in patients treated with basal insulin.

Conditions

Type 2 Diabetes

Keywords

Glucagon; Hypoglycemia; Counterregulation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Lixisenatide

Lixisenatide 20µg daily

Group Type: EXPERIMENTAL

Lixisenatide

Intervention Type: DRUG

Lixisenatide is given for 6 weeks whereafter a hypoglycemia clamp is undertaken

Interventions

Lixisenatide

Lixisenatide is given for 6 weeks whereafter a hypoglycemia clamp is undertaken

Intervention Type: DRUG

Other Intervention Names

Lyxumia

Eligibility Criteria

Inclusion Criteria

1. Male, non-fertile female or female of childbearing potential using a medically approved birth control method aged >18 years.

2. Adult patients with type 2 diabetes treated with basal insulin (NPH insulin, insulin detemir, insulin glargine or insulin degludec) (stable insulin dose (±10%) during the last three months) with concomitant at >3 months stable dose (>1500 mg daily) of metformin.

3. HbA1c <10% (DCCT standard; < 83 mmol(mol) at visit 1.

Exclusion Criteria

1. Treatment with antihyperglycemic agents apart from basal insulin and metformin, i.e., bolus insulin or other antihyperglycemic oral agents apart from metformin

2. Type 1 diabetes (including LADA)

3. Pregnant or lactating female. Women of childbearing potential with no effective contraceptive method. Acceptable contraceptive include contraceptive sponge; hormonal contraception pills, patches, vaginal rings, injectable contraceptives; and intrauterine devices. Women of childbearing potential (pre-menopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative serum pregnancy test at screening visit. They must use an effective contraceptive method throughout the study, and agree to repeat pregnancy tests at designated visits. The applied methods of contraception have to meet the criteria for a highly effective method of birth control according to the "Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95)"

4. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.

5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1

6. Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes or hypoglycemia unawareness

7. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.

8. Treatment with growth hormone and oral or parenteral corticosteroid (> 7 consecutive days of treatment) within 8 weeks prior to visit 1 and thereafter during the whole study period.

9. Use of other investigational drugs within 30 days prior to visit 1.

10. Laboratory findings at the time of screening, including amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN) and P-calcitonin ≥20 pg/ml (5.9 pmol/L).

11. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes).

12. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery

13. Allergic reaction to any GLP-1 receptor agonist or to metacresol

14. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting,

15. Cardiovascular, hepatic, neurological, or endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lund University

OTHER

Sponsor Role: lead

Responsible Party

Bo Ahren

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bo Ahrén, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University

Locations

Clinical Research Department

Malmo, , Sweden

Countries

Sweden

References

Farngren J, Persson M, Ahren B. Effect of the GLP-1 Receptor Agonist Lixisenatide on Counterregulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes. Diabetes Care. 2016 Feb;39(2):242-9. doi: 10.2337/dc15-1274. Epub 2015 Nov 4.

Reference Type: DERIVED

PMID: 26537183 (View on PubMed)

Other Identifiers

2012-004959-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16

Identifier Type: -

Identifier Source: org_study_id