Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antigen-Lipid-Driven Monoclonal Gammopathies Targeting Epicardial Fat

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02920190
Recruitment Status : Not yet recruiting
First Posted : September 30, 2016
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Gianluca Iacobellis, University of Miami

Brief Summary:

Background

Antigen-driven selection has been implicated in the pathogenesis of monoclonal gammopathies. Patients with Gaucher's disease have an increased risk of monoclonal gammopathies and symptomatic myeloma. Clonal immunoglobulin in patients with Gaucher's disease and in mouse models of Gaucher's disease-associated gammopathy are reactive against lyso-glucosylceramide (LGL1), which is markedly elevated in these patients and mice. A recent report indicates that clonal immunoglobulins in 33% of sporadic human monoclonal gammopathies may also be specific for the lysolipids LGL1 and lysophosphatidylcholine. Substrate reduction ameliorates Gaucher's disease-associated gammopathy in mice. This principle (that antigen removal can induce tumor regression) has been proven in other hematologic malignancies, where H. Pylori eradication causes lymphoma regression is a significant group of patients. Thus, as longterm immune activation by lysolipids may underlie both Gaucher's disease-associated gammopathies and some sporadic monoclonal gammopathies, this may represent a focus for treatment.

Epicardial fat (EAT), the visceral fat of the heart, is highly enriched in genes involved in inflammation and lipid metabolism; it activates local and systemic inflammation and innate inflammatory response. EAT is rich in saturated fatty acids and has high protein content, and the greatest capacity for free fatty acids release and uptake among any other visceral fat depots. Of interest, EAT is highly enriched in sphingolipids, including ceramide. EAT clinical measurability with an ultrasound technique, first developed and validated by Iacobellis, and its rapid responsiveness and reduction to medications targeting the visceral fat, such as the glucagon-like peptide 1 analogues (GLP1A), as ongoing clinical trials are demonstrating, is of growing and remarkable interest.

Study Hypothesis

To target EAT, as marker of visceral fat, with GLP1A treatment to modulate/reduce/remove the antigen(s) (lipid/inflammatory/immune) stimulation for patients with monoclonal gammopathies that are lipid targeted.

Study Design

Interventional, single-group, open label pilot study. The investigators will identify monoclonal gammopathy patients whose antibodies are lipid/visceral fat targeted (goal is 10 initially as a pilot) and who are overweight/obese (BMI > 27). Eligible patients will be started on Liraglutide up to 1.8 mg sc once daily, as adjunct weight loss treatment for 12 months.

Study Endpoints

  • Ultrasound measured EAT reduction by at least 20%
  • Improvement in the monoclonal immunoglobulin profile Reduction in plasma ceramide and lipidomics levels

Parameters will be monitored at 3 months, 6 months and 12 months.


Condition or disease Intervention/treatment Phase
Monoclonal Gammopathies Overweight Obesity Drug: Liraglutide Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduction of Antigen-Lipid-Driven Monoclonal Gammopathies by Targeting Epicardial Fat and Its Lipids Content With Liraglutide: A Glucagon Like Peptide-1 Receptor Analogue (GLP-1RA)
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Liraglutide
Eligible patients will be started on Liraglutide up to 1.8 mg sc once daily, as adjunct weight loss treatment for 12 months.
Drug: Liraglutide
Interventional, single-group, open label pilot study. The investigators will identify monoclonal gammopathy patients whose antibodies are lipid/VAT targeted (goal is 10 initially as a pilot) and who are overweight/obese (BMI > 27). Eligible patients will be started on Liraglutide up to 1.8 mg sc once daily, as adjunct weight loss treatment for 12 months.




Primary Outcome Measures :
  1. Ultrasound Epicardial Fat Thickness [ Time Frame: 6-12 months ]
    Epicardial fat thickness (mm) reduction by at least 20%


Secondary Outcome Measures :
  1. Monoclonal gammopathy [ Time Frame: 6-12 months ]
    Changes in serum immunoglobulins

  2. Plasma ceramide [ Time Frame: 6-12 months ]
    Reduction in plasma ceramide levels (mcmol/L)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BMI ≥27 kg/m2
  • At least one overweight/obesity related comorbidity (such as type 2 diabetes, pre-diabetes [IFG, IGT], hypertension, dyslipidemia)
  • Age > 18 and < 70 years old

Exclusion Criteria:

  • Known contra-indications to Liraglutide, such as previous history of pancreatitis or medullary thyroid carcinoma, personal or family history of MEN, in accordance with risks and safety information included in the latest updated Prescribing Information for Victoza®
  • Type 1 diabetes, as defined by American Diabetes Association (ADA) criteria
  • Insulin dependent or treated type 2 diabetes
  • Current use of other injectable incretins
  • History of diabetes ketoacidosis
  • Advanced Chronic Kidney Disease, as defined by Glomerular Filtration Rate (GFR) < 30 mL/min/1.73m2
  • Clinical signs or symptoms of New York Heart Association (NYHA) class III-IV heart failure
  • Clinical or laboratory evidences of chronic active liver diseases
  • Acute or chronic infective diseases
  • Known or suspected allergy to Liraglutide, excipients, or related products
  • Pregnant, breast-feeding or the intention of becoming pregnant
  • Females of childbearing potential who are not using adequate contraceptive methods

Publications:
Layout table for additonal information
Responsible Party: Gianluca Iacobellis, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT02920190     History of Changes
Other Study ID Numbers: 20160568
First Posted: September 30, 2016    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Overweight
Paraproteinemias
Monoclonal Gammopathy of Undetermined Significance
Body Weight
Signs and Symptoms
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hypergammaglobulinemia
Liraglutide
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists