Effect of Liraglutide on Clock Genes

NCT02783196 | Unknown

• 1 other identifier: 0100-16 WOMC
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Clock Gene expression

  The Clock Genes mRNA expression will be assessed in white blood cells

  Up to 95 days

Secondary Outcomes (4)

• AMPK mRNA expression

  Up to 95 days

• SIRT1 mRNA expression

  Up to 95 days

• Beta-cell function

  Up to 92 days

• Overall glycemia

  Up to 95 days

Study Arms (2)

Liraglutide (LIR)

EXPERIMENTAL

Type 2 diabetic randomized to start with two 40 days treatment periods starting with Liraglutide ( IR) treatment, and then after 2 weeks of wash-out, will crossover to second treatment period of 40 days with placebo (PLA)

Drug: Liraglutide

Placebo (PLA)

PLACEBO COMPARATOR

Type 2 diabetic randomized to start with two 40 days treatment periods starting with placebo ( PLA) treatment, and then after 2 weeks of wash-out, will crossover to second treatment period of 40 days with Liraglutide ( LIR)

Drug: Placebo

Interventions

Liraglutide DRUG

In the LIR arm, the participants will be provided with instructions in using pre-filled single-use plastic syringes ready for once daily subcutaneous injection of LIR. From day 1 to day 10, with LIR daily dose of 0.6 mg (0.1 ml), followed by other 10 day courses (from day 11 to day 20) with LIR 1.2 mg (0.2 ml), then will be up-titrated to high dose 1.8 mg (0.3 ml) of LIR (from day 21 to day 40). At crossover-day 40, the participants will undergo a 14 days wash-out period, day 41 to day 55.

Also known as: LIR

Liraglutide (LIR)

Placebo DRUG

In the PLA arm, the participants will be provided with instructions in using pre-filled single-use plastic syringes ready for once daily subcutaneous injection of PLA. Will start with PLA with matched volume saline injections of 0.1 ml PLA during the first 10 days, followed by 10 days, with 0.2 ml PLA, thereafter PLA will be up-titrated to highest volume 0.3 ml placebo for the rest of the PLA treatment period . At crossover-day 40, the participants will undergo a 14 days wash-out period, day 41 to day 55.

Also known as: PLA

Placebo (PLA)

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with T2D diagnosed that were diagnosed \< 20 years.
• HbA1c: 7 to 10 % at screening and at qualification
• BMI: 26-32 kg/m2.
• Men and women
• Between the ages of 30 and 75 years.
• Patients treated with diet alone or diet plus metformin and SGLT2 inhibitors, at a stable dose for at least 3 months.
• Concomitant medication i.e. antihypertensive, anti-lipidemic, anti-thrombotic drugs will be allowed.
• Patients that usually wake up between 06:00 and 07:00 and go to sleep between 22:00 and 24:00.
• 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.
• For woman of child bearing potential, negative pregnancy test and willingness to use birth control during the study :

You may not qualify if:

• Type 1 diabetes or secondary forms of diabetes.
• Use of glucose-lowering therapy apart from metformin and SGLT2 inhibitors.
• Treatment with GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors within the last 3 months.
• Major illness with life expectancy \< 5 years.
• Serum creatinine level \>2mg/d or renal dysfunction: (estimated glomerular filtration rate \<45 mL/min/1.73 m2).
• Hepatic dysfunction: liver disease or transaminase levels \>3-fold above normal.
• History of acute or chronic pancreatitis or high risk for pancreatitis i.e. triglycerides over 400 mg/dl or alcoholism.
• Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma.
• Familial or personal history of multiple endocrine neoplasia type 2 (MEN2), familial or non-familial medullary thyroid carcinoma (MTC)
• Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer).
• Those taking psychotropic, anorectic medication, steroid treatment or with illicit drug abuse or alcoholism within one year prior to study onset.
• Congestive heart failure and all cardiac arrhythmias i.e. atrial fibrillation.
• Pregnancy or lactation.
• Eating disorders and subjects after bariatric surgery or affected by gastroparesis.
• Night or rotating shift workers or those who crossed more than 2 time zones during the 2-week period prior to study onset.

Sponsors & Collaborators

• Tel Aviv University: lead

Study Sites (1)

Diabetes Unit E. Wolfson Hospital

Holon, Tel Aviv, 58100, Israel

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Julio Wainstein, MD

  Diabetes Unit Wolfson Medical center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniela Jakubowicz, MD

CONTACT

972-508105552; daniela.jak@gmail.com

Julio Wainstein, MD

CONTACT

972-506296940; vainstein@wmc.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: May 26, 2016
• Study Start: July 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: June 1, 2017
• Last Updated: May 26, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)