Effect of Liraglutide on Microbiome in Obesity

NCT04046822 | Unknown Phase 4

• 1 other identifier: Microbiome 1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the trial is to assess whether the beneficial effect of liraglutide on weight is mediated by changes in the composition of the intestinal Microbiome. The main mechanisms of action of liraglutide were traced to a reduction in the secretion of glucagon and slowing gastric emptying resulting in decreased appetite and body weight. It also seems that liraglutide is capable of increasing the satiety signals thanks to a dual mechanism of stimulation and inhibition induced by medication. Pomc neurons (opiomelacortin) present in hypothalamic arcuate nuclei, stimulated by liraglutide, glucagon-like peptide- 1 (GLP-1) receptor expressed by inhibiting intensely appetite. At the same time through the GABAergic neuronal activity is inhibited neuropeptide Y(NPY) deputies to the production of orexins that are powerful promoters of appetite. Alterations in the composition of the human gut microbiome occur in metabolic disorders such as obesity, diabetes. Liraglutide has been reported to switch microbiome composition towards lean-related bacterial phylotypes in animal studies. This leads to hypothesize that the switch of microbiome by liraglutide may be one of the mechanisms through which liraglutide may exert its effect. In particular the investigators hypothesize that liraglutide could restore a healthy microbiome or at least improve the microbiome composition through slowing gastrointestinal motility. Moreover, the liraglutide-related change of microbiome could be an additional mechanism that contribute to the beneficial metabolic effect of liraglutide. To test this hypothesis the investigators will investigate if there will be any change of gut microbiome assessed as Firmicutes-to-Bacteroidetes ratio after liraglutide treatment. In order to understand if the change of gut microbiome after liraglutide treatment occurs as an association or contributes to the effect of liraglutide ,the investigators will correlate the Firmicutes-to-Bacteroidetes ratios with the changes of Body Mass Index, Body Composition, appetite parameters, chronic inflammation parameters, lipid profile and insulin resistance. All the subjects will follow the same diet in order to avoid any bias.

Conditions

Obesity; Weight Loss; Microbiome

Keywords

obesity; liraglutide; gut microbiome

Outcome Measures

Primary Outcomes (1)

• Change in gut microbiome composition assessed by Firmicutes-to-Bacteroidetes ratio using Quantitative polymerase chain reaction (PCR)

  The liraglutide treatment effect on gut microbiome composition quantified as Firmicutes-to-Bacteroidetes ratio by Quantitative polymerase chain reaction (PCR)

  Change from baseline in gut microbiome composition at weeks 5 (visit 7)

Secondary Outcomes (20)

• Change in body weight (kg) assessed by scale

  Change from baseline in body weight at weeks 5 (visit 7)

• Change in body weight (kg) that will be combined with height (m) to report BMI (kg/m^2) where kg is a person's weight in kilograms and m2 is a person's height in metres squared

  Change from baseline in body mass index at weeks 5 (visit 7)

• Change in body composition assessed by Bioelectrical impedance analysis (BIA)

  Change from baseline in body composition at weeks 5 (visit 7)

• Change in hormonal regulation of appetite assessed by ghrelin levels

  Change from baseline in ghrelin levels at weeks 5 (visit 7)

• Change in hormonal regulation of hunger suppression assessed by cholecystokinin levels

  Change from baseline in cholecystokinin levels at weeks 5 (visit 7)

Study Arms (2)

Active drug

ACTIVE COMPARATOR

Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.

Drug: Liraglutide 6 MG/ML [Saxenda]

Placebo

PLACEBO COMPARATOR

Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.

Drug: Placebo

Interventions

Liraglutide 6 MG/ML [Saxenda] DRUG

Liraglutide is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the liraglutide dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.

Also known as: Saxenda

Active drug

Placebo DRUG

Placebo is administered once daily by subcutaneous injections with the pen-injector, either in the abdomen, thigh or upper arm. Injections can be done at any time of day irrespective of meals. Subjects will be instructed to escalate the placebo dose to 3.0 mg/day over a 4 week period following an initial dose of 0.6 mg/day and weekly dose escalation steps of 0.6 mg/day.

Also known as: Saline Injection

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial;
• Age ≥ 18 years and \< 65 years at the time of signing informed consent;
• Body mass index (BMI) ≥ 30 kg/m2
• Stable body weight during the previous 3 months (\< 5 kg self-reported weight change).

You may not qualify if:

• General Safety
• Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial;
• Current use or use within three months before this trial of GLP-1 receptor agonist, pramlintide, sibutramine, orlistat, zonisamide, topiramate or phentermine;
• Type 1 diabetes;
• Type 2 diabetes;
• Obesity related to endocrine diseases;
• Hepatic Failure (AST and/or ALT \>3 times upper limit of normal and/or Total Bilirubin \>1.7 upper limit of normal)
• End stage renal disease (eGFR \< 30 ml/min/1.73 m2 ) or chronic or intermittent haemodialysis or peritoneal dialysis
• History or presence of chronic pancreatitis
• Presence of acute pancreatitis within the past 180 days prior to the day of screening
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening
• Severe psychiatric disorder which in the investigator's opinion could compromise compliance with the protocol
• Known or suspected hypersensitivity to trial product(s) or related products
• Previous participation in this trial. Participation is defined as randomisation

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

"Federico II" University of Naples, Department of Clinical and Molecular Endocrinology and Oncology

Naples, 80131, Italy

RECRUITING

Related Publications (5)

• Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005 Jun 10;308(5728):1635-8. doi: 10.1126/science.1110591. Epub 2005 Apr 14.

  PMID: 15831718 BACKGROUND

• Patterson E, Ryan PM, Cryan JF, Dinan TG, Ross RP, Fitzgerald GF, Stanton C. Gut microbiota, obesity and diabetes. Postgrad Med J. 2016 May;92(1087):286-300. doi: 10.1136/postgradmedj-2015-133285. Epub 2016 Feb 24.

  PMID: 26912499 BACKGROUND

• Dinan TG, Cryan JF. Mood by microbe: towards clinical translation. Genome Med. 2016 Apr 6;8(1):36. doi: 10.1186/s13073-016-0292-1.

  PMID: 27048547 BACKGROUND

• Nakatani Y, Maeda M, Matsumura M, Shimizu R, Banba N, Aso Y, Yasu T, Harasawa H. Effect of GLP-1 receptor agonist on gastrointestinal tract motility and residue rates as evaluated by capsule endoscopy. Diabetes Metab. 2017 Oct;43(5):430-437. doi: 10.1016/j.diabet.2017.05.009. Epub 2017 Jun 23.

  PMID: 28648835 BACKGROUND

• Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. doi: 10.1073/pnas.0407076101. Epub 2004 Oct 25.

  PMID: 15505215 BACKGROUND

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Liraglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Annamaria Colao, MD

CONTACT

00390817462132; colao@unina.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: August 6, 2019
• Study Start: January 9, 2019
• Primary Completion: January 9, 2020
• Study Completion: April 30, 2020
• Last Updated: August 20, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)