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Trial record 3 of 7 for:    RORA

Effect of Liraglutide on Clock Genes (LIR-CG)

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ClinicalTrials.gov Identifier: NCT02783196
Recruitment Status : Unknown
Verified May 2016 by Daniela Jakubowicz, Tel Aviv University.
Recruitment status was:  Not yet recruiting
First Posted : May 26, 2016
Last Update Posted : May 26, 2016
Sponsor:
Information provided by (Responsible Party):
Daniela Jakubowicz, Tel Aviv University

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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Liraglutide Drug: Placebo Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Advantages of Liraglutide Mediated Through Its Effect on Clock Gene mRNA Expression
Study Start Date : July 2016
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Experimental: Liraglutide (LIR)
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
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.
Other Name: LIR

Placebo Comparator: Placebo (PLA)
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
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.
Other Name: PLA




Primary Outcome Measures :
  1. Clock Gene expression [ Time Frame: Up to 95 days ]
    The Clock Genes mRNA expression will be assessed in white blood cells


Secondary Outcome Measures :
  1. AMPK mRNA expression [ Time Frame: Up to 95 days ]
    he AMPK mRNA expression will be assessed in white blood cells on day 0, on day 40 and on day 95

  2. SIRT1 mRNA expression [ Time Frame: Up to 95 days ]
    SIRT1 mRNA expression will be assessed in white blood cells on day 0, on day 40 and on day 95

  3. Beta-cell function [ Time Frame: Up to 92 days ]
    Beta-cell function based on oral glucose tolerance test (OGTT) will be assessed on day -3, on day 37 and on day 92

  4. Overall glycemia [ Time Frame: Up to 95 days ]
    Overall glycemia assessed with continuous glucose monitoring system (CGMS) will be performed during 3 days at baseline from day - 3 to day 0, again from day 37 to 40 and three days before the end of intervention from day 92 to day 95



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02783196


Contacts
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Contact: Daniela Jakubowicz, MD 972-508105552 daniela.jak@gmail.com
Contact: Julio Wainstein, MD 972-506296940 vainstein@wmc.gov.il

Locations
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Israel
Diabetes Unit E. Wolfson Hospital
Holon, Tel Aviv, Israel, 58100
Sponsors and Collaborators
Tel Aviv University
Investigators
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Principal Investigator: Julio Wainstein, MD Diabetes Unit Wolfson Medical center

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Responsible Party: Daniela Jakubowicz, Prof, Tel Aviv University
ClinicalTrials.gov Identifier: NCT02783196     History of Changes
Other Study ID Numbers: 0100-16 WOMC
First Posted: May 26, 2016    Key Record Dates
Last Update Posted: May 26, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists