Effect of Liraglutide on Clock Genes

• Status: Unknown status
• Trial end date: 2017-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is undertaken to search whether glucagon-like peptide-1 (GLP-1) analogue, Liraglutide, by enhancing clock gene and AMPK-SIRT-1 mRNA expression, may reverse the metabolic abnormalities of type 2 diabetes, improving overall glycemic excursion, inflammatory cytokines and β-cell function in type 2 diabetes individuals.

The investigators aim is to compare the effect of 40 days treatment with Liraglutide (LIR) vs. 40 days with placebo (PLA) in T2D participants on the following end points:

Primary end-points:

• Change in the oscillation of CG (i.e. CLOCK, BMAL1, Per1, Per2, Cry1, Cry2, Rev-erb-alpha Ror-alpha), AMPK, SIRT1 and inflammatory cytokines mRNA expression in white blood cells (WBCs).

Secondary end-points:

• Overall daily glycemic variation assessed with continuous glucose monitoring system (CBMS)

• Serum levels of inflammatory cytokines (TNF-α, IL-1β, IL-6)

• β-Cell function derived from glucose and insulin response to OGTT

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tel Aviv University
• Treatments: Liraglutide

Criteria

Inclusion Criteria

1. Patients with T2D diagnosed that were diagnosed < 20 years.

2. HbA1c: 7 to 10 % at screening and at qualification

3. BMI: 26-32 kg/m2.

4. Men and women

5. Between the ages of 30 and 75 years.

6. Patients treated with diet alone or diet plus metformin and SGLT2 inhibitors, at a stable dose for at least 3 months.

7. Concomitant medication i.e. antihypertensive, anti-lipidemic, anti-thrombotic drugs will be allowed.

8. Patients that usually wake up between 06:00 and 07:00 and go to sleep between 22:00 and 24:00.

9. Subjects should not have shift work within 6 month of the study and should not have crossed time zones within 1 month of the study.

10. For woman of child bearing potential, negative pregnancy test and willingness to use birth control during the study :

Exclusion Criteria:

1. Type 1 diabetes or secondary forms of diabetes.

2. Use of glucose-lowering therapy apart from metformin and SGLT2 inhibitors.

3. Treatment with GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors within the last 3 months.

4. Major illness with life expectancy < 5 years.

5. Serum creatinine level >2mg/d or renal dysfunction: (estimated glomerular filtration rate <45 mL/min/1.73 m2).

6. Hepatic dysfunction: liver disease or transaminase levels >3-fold above normal.

7. History of acute or chronic pancreatitis or high risk for pancreatitis i.e. triglycerides over 400 mg/dl or alcoholism.

8. Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma.

9. Familial or personal history of multiple endocrine neoplasia type 2 (MEN2), familial or non-familial medullary thyroid carcinoma (MTC)

10. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer).

11. Those taking psychotropic, anorectic medication, steroid treatment or with illicit drug abuse or alcoholism within one year prior to study onset.

12. Congestive heart failure and all cardiac arrhythmias i.e. atrial fibrillation.

13. Pregnancy or lactation.

14. Eating disorders and subjects after bariatric surgery or affected by gastroparesis.

15. Night or rotating shift workers or those who crossed more than 2 time zones during the 2-week period prior to study onset.

16. No change in medication or nutrition supplements or physical activity will be made during the study period.

17. Known proliferative retinopathy or maculopathy