Study on Lixisenatide and Counterregulation to Hypoglycemia

• ClinicalTrials.gov Identifier: NCT02020629
• Recruitment Status: Completed
• First Posted: December 25, 2013
• Last Update Posted: December 15, 2015
• Sponsor: Lund University
• Information provided by (Responsible Party): Bo Ahren, Lund University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Drug: Lixisenatide	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Lixisenatide on Glucagon Secretion During Hypoglycemia in Patients With Insulin-treated Type 2 Diabetes
• Study Start Date: December 2013
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lixisenatide; Lixisenatide 20µg daily	Drug: Lixisenatide; Lixisenatide is given for 6 weeks whereafter a hypoglycemia clamp is undertaken; Other Name: Lyxumia

Outcome Measures

Primary Outcome Measures :

1. Glucagon response to hypoglycemia [ Time Frame: 30 min ]
   Hypoglycemia is induced by clamp during 30 min; glucagon levels are measured during this time frame

Secondary Outcome Measures :

1. Cortisol response to hypoglycemia [ Time Frame: 30 min ]
   Hypoglycemia is induced by a clamp during 30 min. Cortisol is measured during this time frame.
2. Catecholamines [ Time Frame: 30 min ]
   Hypoglycemia is induced by a clamp during 30 min. Catecholamines are measured during this time frame.

Other Outcome Measures:

1. HbA1c [ Time Frame: 6 weeks ]
   Change in HbA1c during six weeks treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Sweden

Clinical Research Department

Malmö, Sweden, 20502

Sponsors and Collaborators

Lund University

Investigators

• Principal Investigator: Bo Ahrén, MD, PhD; Lund University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Farngren J, Persson M, Ahrén 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.

• Responsible Party: Bo Ahren, Professor, Lund University
• ClinicalTrials.gov Identifier: NCT02020629
• Other Study ID Numbers: 16; 2012-004959-36 ( EudraCT Number )
• First Posted: December 25, 2013
• Last Update Posted: December 15, 2015
• Last Verified: December 2015

Keywords provided by Bo Ahren, Lund University:

Glucagon; Hypoglycemia; Counterregulation

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Hypoglycemia; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lixisenatide; Hypoglycemic Agents; Physiological Effects of Drugs