The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes

• Status: Unknown status
• Trial end date: 2020-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to conduct an interventional, one year, randomized, double blind, placebo-controlled trial with Liraglutide in patients with type 2 diabetes (diabetes duration of >6 months and <10 years, HbA1c <10%) to evaluate its effects on the peripheral autonomic nervous system, as well as inflammatory markers, and measures of oxidative and nitrosative stress.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eastern Virginia Medical School
• Treatments: Liraglutide

Criteria

Inclusion Criteria:

1. established type 2 diabetes (diabetes duration of >6 months and <10 years).

2. Age 18-80 years

3. HbA1c at screening ≤ 10%

4. Subjects on stable (≥3 months prior to Screening) Standard of Care background diabetic therapy. Diabetic treatment regimens include diet and exercise alone or in association with oral anti-diabetic drugs (monotherapy or combinations) and/or long-acting insulin.

Exclusion Criteria:

1. Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml, <35y and prone to ketoacidosis)

2. Treatment with rapid-acting or short-acting insulin within the last 3 months

3. Proliferative retinopathy or maculopathy requiring acute treatment

4. Impaired renal function , defined as serum creatinine ≥ 125 µmol/L (≥1.4 mg/dL) for males and ≥ 110 µmol/L (≥1.24 mg/dL) for females

5. Impaired liver function, defined as aspartate transaminase (AST) or alanine transaminase (ALT), ≥ 2.5 times the upper limit of normal

6. Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non-diabetic origin

7. Uncontrolled treated/untreated hypertension (systolic blood pressure (BP) ≥180 or diastolic blood pressure (BP) ≥100 at screening)

8. Clinically significant active macrovascular disease including myocardial infarction or cerebrovascular event within the past 6 months. Other exclusions include coronary artery bypass graft or coronary angioplasty in the previous 3 months, unstable angina pectoris (chest pain at rest, worsening chest pain, or admission to the emergency room (ER) or hospital for chest pain) within the previous 3 months, and/or congestive heart failure (NYHA Class III-IV)

9. Subjects known to be Hepatitis B surface antigen or Hepatitis C antibody positive with active hepatitis.

10. Active infection (e.g., human immunodeficiency virus (HIV), hepatitis), or a history of severe infection during the 30 days prior to screening

11. Evidence of immunocompromised status, including but not limited to individuals who have undergone organ transplantation, who are known to be HIV positive, or who are taking immunosuppressive drugs or chronic systemic corticosteroid treatment.

12. Major surgical procedure during the 30 days prior to screening

13. Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years

14. Known clinically significant gastric emptying abnormality (e.g. severe gastroparesis), or history of gastric bypass (bariatric) surgery

15. Thyroid stimulating hormone (TSH) outside of normal limits at screening, or presence of a thyroid nodule detected on physical examination that has not been fully evaluated

16. Thyroid hormone therapy that has not been stable for ≥6 weeks prior to Screening

17. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN-2)

18. History of acute or chronic pancreatitis

19. Subjects taking medications that are known to affect autonomic function need to be at a stable dose of those medications ≥ 3 months prior to inclusion in the study

20. Other clinically significant, active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary or hematological system that, in the opinion of the investigator, would compromise the subject's participation in the study, might confound the results of the study or pose additional risk in administering the study drug

21. Recurrent severe hypoglycemia and/or hypoglycemia unawareness.

22. Concurrent participation in another clinical trial with use of an experimental drug or device within 30 days of study entry.

23. Known or suspected history of alcohol or substance abuse

24. Mental incapacity, unwillingness or language barrier precluding adequate understanding of or cooperation with the study.

25. Women of childbearing potential (WOCBP*) who are pregnant, breast-feeding or intend to become pregnant

26. WOCBP* must have a negative pregnancy test at Screening and must agree to use adequate contraceptive methods** during the study and for one additional menstrual cycle following the end-of-treatment visit

27. Known or suspected hypersensitivity to study product(s) or related products

28. Patients with low vitamin B12 levels will be excluded

29. Current use or use 6 months prior to study participation of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon like peptide-1 (GLP-1) agonists will be excluded

30. Liraglutide has not been studied in combination with prandial insulin. Patients who use prandial insulin may be excluded