Determine the Frequency of Variants in the GBA/PSAP Genes in Patients With MM or MGUS (GAMY)

Determine the Frequency of Variants in the GBA/PSAP Genes in Patients With Multiple Myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS)

No effective specific treatment is currently available for the management of Multiple Myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS). A better understanding of the pathophysiological mechanisms would make it possible to propose treatments specifically targeting the deregulated pathways.

Study Overview

• Status: Not yet recruiting
• Conditions: Monoclonal Gammopathy of Undetermined Significance; Myeloma Multiple
• Intervention / Treatment: Biological: Evaluation of the presence and number of mutated alleles of the GBA/PSAP genes in patients with MM or MGUS

Detailed Description

This study will characterise the links between rare diseases and complex, chronic diseases. Metabolism can be visualised as a complex network in which the various biomolecules represent metabolic nodes and are linked together by connections. The number of connections at a node influences the effect of that biomolecule on the metabolic network(s) as a whole. If a biomolecule has a large number of connections, altering a metabolic pathway involving it will have an effect that will spread throughout the network. On the other hand, metabolic pathways with a high flux have a major impact on the homeostasis of the network. Thus, alteration of such a metabolic pathway cannot be without consequence: a major alteration could induce a rare hereditary metabolic disease with an early-onset clinic, whereas an alteration with a moderate effect could participate in the pathogenesis of complex diseases, and may open up new therapeutic prospects for these tumour pathologies.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Soumeya BEKRI, Pr; Phone Number: +33 02 32 88 81 24; Email: soumeya.bekri@chu-rouen.fr
• Study Contact Backup: Name: Abdellah AB TEBANI, Pr; Phone Number: +33 02 32 88 81 24; Email: Abdellah.Tebani@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

100 patients with multiple myeloma (MM), 100 patients with monoclonal gammopathy of undetermined significance (MGUS), 100 controls with plasma samples available

Description

Inclusion Criteria:

• Major patients with multiple myeloma (MM) (defined by clonal proliferation of tumour plasma cells (>10%), presence of a monoclonal peak in serum or urine (excluding non-secretory myeloma) and organ involvement secondary to bone marrow invasion) or with MGUS (defined as bone marrow plasmacytosis of less than 10%, associated with a monoclonal protein of less than 30g/L and no clinical involvement).
• Membership of a social security scheme
• Adult having read and understood the information letter and signed the consent form

Exclusion Criteria:

• Person deprived of liberty by an administrative or judicial decision or person placed under court protection / sub-guardianship or guardianship

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Multiple myeloma (MM) patient group; patients with multiple myeloma (MM) (defined by a clonal proliferation of tumour plasma cells (>10%), the presence of a monoclonal peak in the serum or urine (excluding non-secretory myeloma) and organ damage secondary to bone marrow invasion)	Biological: Evaluation of the presence and number of mutated alleles of the GBA/PSAP genes in patients with MM or MGUS; Estimation of the frequency of variants in the PSAP/GBA genes in patients with MM or MGUS, then comparison with a reference frequency from databases such as the Exome Aggregation Consortium, the Exome Sequencing Project, the 1000 Genomes Project and the dbSNP.; Other Names: Evaluation of plasma concentrations of LGL1 in patients with MM or MGUS compared to controls; Evaluation of the % Reactivity of plasma immunoglobulins from patients with MM or MGUS towards LGL1
Monoclonal gammopathy of undetermined significance (MGUS) patient group; patients with MGUS (defined as bone marrow plasmacytosis of less than 10%, associated with a monoclonal protein of less than 30g/L and no clinical involvement)	Biological: Evaluation of the presence and number of mutated alleles of the GBA/PSAP genes in patients with MM or MGUS; Estimation of the frequency of variants in the PSAP/GBA genes in patients with MM or MGUS, then comparison with a reference frequency from databases such as the Exome Aggregation Consortium, the Exome Sequencing Project, the 1000 Genomes Project and the dbSNP.; Other Names: Evaluation of plasma concentrations of LGL1 in patients with MM or MGUS compared to controls; Evaluation of the % Reactivity of plasma immunoglobulins from patients with MM or MGUS towards LGL1
Control group; patient with no pathology under study relating to the project	Biological: Evaluation of the presence and number of mutated alleles of the GBA/PSAP genes in patients with MM or MGUS; Estimation of the frequency of variants in the PSAP/GBA genes in patients with MM or MGUS, then comparison with a reference frequency from databases such as the Exome Aggregation Consortium, the Exome Sequencing Project, the 1000 Genomes Project and the dbSNP.; Other Names: Evaluation of plasma concentrations of LGL1 in patients with MM or MGUS compared to controls; Evaluation of the % Reactivity of plasma immunoglobulins from patients with MM or MGUS towards LGL1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of variants in the GBA/PSAP genes in patients with MM or MGUS	The main aim of the research is to determine the frequency of variants in the GBA/PSAP genes in patients with MM or MGUS.	inclusion (one day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of LGL1 in patients with MM or MGUS	Compare the plasma concentration of LGL1 in MM and MGUS patients versus control individuals	inclusion (one day)
Reactivity of monoclonal antibodies in MM and MGUS patients	Assess the % (proportion of patients with reactivity (% reactivity greater than 0) and those without (% reactivity equal to 0)) of reactivity of monoclonal antibodies from MM and MGUS patients to LGL1	inclusion (one day)

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): October 2, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Blood Protein Disorders; Hemorrhagic Disorders; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Immunologic Factors; Physiological Effects of Drugs; Immunoglobulins
• Other Study ID Numbers: 2020/0430/OB; 2022-A00306-37 (Registry Identifier: French Minister)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No