Immunoglobulin Deficiency a Treatable Cause of Fatigue in Patients With Multiple Sclerosis (MS)?

NCT ID: NCT05357781

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 106 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2026-12-30

Brief Summary

The investigators hypothesize that hypogammaglobulinemia (defined as IgG serum concentration <7.0g/L) is a treatable cause of fatigue in people with MS:

The primary objective is to prove the link between hypogammaglobulinemia and fatigue in patients with multiple sclerosis.

The secondary objective is to show that fatigue is mediated via frequent infections in people with MS and hypogammaglobulinemia.

Detailed Description

Multiple sclerosis (MS) is the most common cause of mental and physical disability in young adults affecting approximately 10'000-15'000 persons in Switzerland (incidence 16/100000; prevalence 190/100000). MS-fatigue affects at least 75% of the MS-patients (affected persons in Switzerland 7500-11250). MS-related fatigue has socioeconomic consequences leading to increased sick leaves and a higher probability of unemployment. Effective treatment strategies for MS-fatigue are missing, despite the appearance of more effective immunotherapies to treat autoimmune neuroinflammation and to control MS disease activity. The reason for the lack of therapeutic options is the unclear pathophysiological mechanism of fatigue with many non-MS associated influencing factors like thyroid dysfunction and anaemia.

Fatigue is also present in other inflammatory diseases, cancers and immunodeficiency syndromes. Regarding the latter patients with primary immunodeficiencies (PIDs) and common variable immunodeficiency (CVID) suffer from fatigue in 30 - 76%, which is more common than in the normal population. Studies investigating immunoglobulin replacement therapy in patients with CVID demonstrated a correlation between the frequency of infusions / s.c. applications and wear-off effect/fatigue.

Immunoglobulin deficiency seems to be much more common in people with autoimmune diseases. In MS reduced serum immunglobulin G (IgG) concentrations regardless of immunotherapy affect between 8 - 26% of the patients. Nonetheless consequences of IgG hypogammaglobulinemia in MS are partly unknown. However, based on the findings in patients with CVID, fatigue might be one of them. To close this knowledge gap prospective observational studies are needed.

Conditions

Hypogammaglobulinemia; Multiple Sclerosis; Fatigue

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

MS patients with IgG deficiency (serum IgG-concentration <7g/L).

MS patients with IgG deficiency (serum IgG-concentration \<7g/L).

Laboratory test

Intervention Type: DIAGNOSTIC_TEST

Frequency of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency

MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L).

MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L).

Laboratory test

Intervention Type: DIAGNOSTIC_TEST

Frequency of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency

Interventions

Laboratory test

Frequency of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Fatigue Score

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Multiple Sclerosis following McDonald 2017-Criteria
• Age 18-65 years
• Stable MS disease at inclusion (definition: no clinical relapse, no MRI activity, stable disability within the last 12 months)
• Unchanged immunotherapy within the last 12 months
• Expanded Disability Status Scale (EDSS) level <4 points indicating fully ambulatory patients.
• Capability of written informed consent

Exclusion Criteria

• Severe depression (definition: Beck Depression Index-II (BDI-II) ≥29 points) or other established psychiatric diagnosis
• Immunodeficiency other than hypogammaglobulinemia
• Immunglobulin replacement therapy or indication for immunoglobulin replacement therapy
• Severe Sleepiness (definition: Epworth-Sleepiness-Scale (ESS) >16 points)
• Fatigue aggravating factors such: liver/renal/thyroid dysfunction, substance abuse, medication (tranquilizers /antiepileptics/psychopharmaceuticals), chronic infectious disease (like hepatitis/HIV).
• Other neurodegenerative/autoimmune disease.
• Patients not able to give written consent
• Vulnerable patients such as children, pregnant women and prisoners

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lara Diem, MD

Role: PRINCIPAL_INVESTIGATOR

Inselspital University Hospital of Bern

Locations

University Hospital of Bern Inselspital

Bern, Canton of Bern, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Lara Diem, MD

Role: CONTACT

larafrancesca.diem@insel.ch

0041316327000

Facility Contacts

Lara Diem, MD

Role: primary

larafrancesca.diem@insel.ch

0041316327000

Other Identifiers

2021-02372

Identifier Type: -

Identifier Source: org_study_id