Investigating the Pathogenic Role of N-glycosylation in AL Amyloidosis: Molecular Bases, Diagnosis, and Treatment

NCT07448779 | Recruiting

• 1 other identifier: 2023-1731-GlycAL
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Immunoglobulin light chain (AL) amyloidosis is caused by a typically small, minimally proliferating bone marrow plasma cell clone secreting a patient-unique, unstable, aggregation-prone, toxic light chain (LC). The amyloidogenicity of LCs is encrypted in their sequence, yet molecular determinants of LC pathogenicity remain obscure. N-glycosylation has been long suspected to be a determinant of LC amyloidogenicity based on anecdotal reports of individual AL patients with a clonal LC displaying this post-translational modification. It is hypothesized that N-glycosylation fundamentally contributes to determining the amyloidogenicity of immunoglobulin LCs in a subset of patients with AL and might influence its clinical phenotype. It is further proposed that the synthesis and secretion of unstable LCs that also have to be N-glycosylated might reverberate on the biology of the plasma cell clone, possibly modulating the sensitivity toward different drugs and might represent itself a therapeutic target. The objective of our study is now to elucidate the molecular role of LC N-glycosylation in AL amyloidosis, exploit it for risk assessment, and define its potential impact on the biology of the underlying plasma cell clone and its drug sensitivity.

Conditions

AL Amyloidosis; MGUS; Multiple Myeloma; Monoclonal Gammopathies

Outcome Measures

Primary Outcomes (1)

• Dataset of full-length LC variable region sequences

  Generation of a clinically annotated dataset of full-length immunoglobulin light chain (LC) variable region sequences derived from the largest reported series of patients with AL and MGUS, including clonal characterization and clinical annotation.

  two years

Secondary Outcomes (3)

• Clinical correlates of LC N-glycosylation

  two years

• Refinement of sequence-based prediction of LC amyloidogenicity

  two years

• Biologic and pharmacologic correlates of LC N-glycosylation

  two years

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Treatment-naïve patients with AL amyloidosis or other monoclonal gammopathies

You may qualify if:

• Diagnosis of monoclonal gammopathy (e.g. AL amyloidosis, MGUS, MM, others)
• Planned peripheral blood sampling +/- bone marrow aspiration
• Age \> 18 years
• Willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes through signing a written informed consent.

You may not qualify if:

• Lack of monoclonal gammopathy
• Patients fulfilling the criteria for complete hematologic response after anti-clonal therapy
• Age \<18 years
• Failure to show willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, PV, 27100, Italy

RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Paraproteinemias

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Alice Nevone

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 4, 2026
• Study Start: November 17, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-02

Locations

IT (1)