Antigen-Lipid-Driven Monoclonal Gammopathies Targeting Epicardial Fat
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|ClinicalTrials.gov Identifier: NCT02920190|
Recruitment Status : Not yet recruiting
First Posted : September 30, 2016
Last Update Posted : February 15, 2019
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.
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.
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.
- 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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
Eligible patients will be started on Liraglutide up to 1.8 mg sc once daily, as adjunct weight loss treatment for 12 months.
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.
- Ultrasound Epicardial Fat Thickness [ Time Frame: 6-12 months ]Epicardial fat thickness (mm) reduction by at least 20%
- Monoclonal gammopathy [ Time Frame: 6-12 months ]Changes in serum immunoglobulins
- Plasma ceramide [ Time Frame: 6-12 months ]Reduction in plasma ceramide levels (mcmol/L)