Study on Lixisenatide and Counterregulation to Hypoglycemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Lund University
Sponsor:
Information provided by (Responsible Party):
Bo Ahren, Lund University
ClinicalTrials.gov Identifier:
NCT02020629
First received: December 16, 2013
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Type 2 Diabetes
Drug: Lixisenatide
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effect of Lixisenatide on Glucagon Secretion During Hypoglycemia in Patients With Insulin-treated Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Lund University:

Primary Outcome Measures:
  • Glucagon response to hypoglycemia [ Time Frame: 30 min ] [ Designated as safety issue: No ]
    Hypoglycemia is induced by clamp during 30 min; glucagon levels are measured during this time frame


Secondary Outcome Measures:
  • Cortisol response to hypoglycemia [ Time Frame: 30 min ] [ Designated as safety issue: No ]
    Hypoglycemia is induced by a clamp during 30 min. Cortisol is measured during this time frame.

  • Catecholamines [ Time Frame: 30 min ] [ Designated as safety issue: No ]
    Hypoglycemia is induced by a clamp during 30 min. Catecholamines are measured during this time frame.


Other Outcome Measures:
  • HbA1c [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Change in HbA1c during six weeks treatment


Estimated Enrollment: 18
Study Start Date: December 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lixisenatide
Lixisenatide 20µg daily
Drug: Lixisenatide
Lixisenatide is given for 6 weeks whereafter a hypoglycemia clamp is undertaken
Other Name: Lyxumia

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02020629

Contacts
Contact: Bo Ahrén, MD, PhD +46462220758 Bo.Ahren@med.lu.se
Contact: Margaretha Persson, MD ´+4640332037 Margaretha.Persson@med.lu.se

Locations
Sweden
Clinical Research Department Recruiting
Malmö, Sweden, 20502
Contact: Bo Ahrén, MD, PhD    +46462220758    Bo.Ahren@med.lu.se   
Contact: Margaretha Persson, PhD    +4640332037    Margaretha.Persson@med.lu.se   
Principal Investigator: Bo Ahrén, MD, PhD         
Sponsors and Collaborators
Lund University
Investigators
Principal Investigator: Bo Ahrén, MD, PhD Lund University
  More Information

No publications provided

Responsible Party: Bo Ahren, Professor, Lund University
ClinicalTrials.gov Identifier: NCT02020629     History of Changes
Other Study ID Numbers: 16, 2012-004959-36
Study First Received: December 16, 2013
Last Updated: December 19, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by Lund University:
Glucagon
Hypoglycemia
Counterregulation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 24, 2014