HypogammaglobulinemiaFatIgGNCT05357781
Immunoglobulin Deficiency a Treatable Cause of Fatigue in Patients With Multiple Sclerosis (MS)?
An observational study of Hypogammaglobulinemia and Multiple Sclerosis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypogammaglobulinemia, Multiple Sclerosis, Fatigue
- What is being tested?
- Laboratory test
- How many people
- 106 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jul 2022to 30 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Multiple Sclerosis Patients
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital of Bern Inselspital
Bern, Canton of Bern, 3010
Lara Diem, MD, 0041316327000, larafrancesca.diem@insel.ch
About this study
Official title: Immunoglobulin Deficiency a Treatable Cause of Fatigue in Patients With Multiple Sclerosis (MS)? - A Prospective Observational Fatigue Trial
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.
Read the 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
- Being tested
- Laboratory test
- Keywords
- Fatigue, Hypogammaglobulinemia
- Medical subject headings
- Agammaglobulinemia, Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory testDiagnostic test
Also called Fatigue Score
Frequency of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency
| Study group | Role | What they receive |
|---|---|---|
| MS patients with IgG deficiency (serum IgG-concentration <7g/L). | MS patients with IgG deficiency (serum IgG-concentration <7g/L). Receives: Diagnostic Test: Laboratory test | |
| MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L). | MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L). Receives: Diagnostic Test: Laboratory test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with fatigue and hypogammaglobulinemia
The primary endpoint will be measured as frequency (%) of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency (IgG serum concentration <7.0 g/L) compared to those with normal IgG-serum concentration (≥ 7.0 g/L).
The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue) FSMC Sum Score: ≥ 43 points mild fatigue, ≥ 53 points moderate fatigue, ≥ 63 severe fatigue
Measured: 1.5 years
Number of patients with fatigue without hypogammaglobulinemia
The primary endpoint will be measured as frequency (%) of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency (IgG serum concentration <7.0 g/L) compared to those with normal IgG-serum concentration (≥ 7.0 g/L).
The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue) FSMC Sum Score: ≥ 43 points mild fatigue, ≥ 53 points moderate fatigue, ≥ 63 severe fatigue
Measured: 1.5 years
Secondary outcomes (1)
Fatigue and infections
As secondary endpoint the frequency of infections (infection/months) in MS patients will be measured and compared between those with (IgG serum concentration <7.0 g/L) and without hypogammaglobulinemia (IgG serum concentration ≥ 7.0 g/L). Furthermore, the mediation of fatigue by "frequency of infections*" will be detailed in the cohort of MS patients with hypogammaglobulinemia.
*A telephone interview with 6 questions about the frequency of infections will take place once a month.
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start1 Jul 2022
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypogammaglobulinemiaStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lara Diem, MD, Principal investigator, Inselspital University Hospital of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05357781
- Sponsor's protocol ID
- 2021-02372
- Acronym
- FatIgG
- Status last verified
- Apr 2026
- First submitted
- 19 Apr 2022
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunoglobulin Deficiency a Treatable Cause of Fatigue in Patients With Multiple Sclerosis (MS)? - A Prospective Observational Fatigue Trial
- ClinicalTrials.gov ID
- NCT05357781
- Acronym / sponsor ID
- FatIgG / 2021-02372
- Conditions
- Hypogammaglobulinemia, Multiple Sclerosis, Fatigue
- Keywords
- Fatigue, Hypogammaglobulinemia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 3 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MS patients with IgG deficiency (serum IgG-concentration <7g/L). | – | Diagnostic Test: Laboratory testMS patients with IgG deficiency (serum IgG-concentration <7g/L). |
| MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L). | – | Diagnostic Test: Laboratory testMS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Multiple Sclerosis Patients
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory testAlso: Fatigue ScoreFrequency of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency | Diagnostic test | MS patients with IgG deficiency (serum IgG-concentration <7g/L)., MS patients with normal IgG serum concentration (serum IgG-concentration ≥7g/L). |
Primary outcome
Number of patients with fatigue and hypogammaglobulinemia
Time frame: 1.5 years
The primary endpoint will be measured as frequency (%) of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency (IgG serum concentration <7.0 g/L) compared to those with normal IgG-serum concentration (≥ 7.0 g/L). The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue) FSMC Sum Score: ≥ 43 points mild fatigue, ≥ 53 points moderate fatigue, ≥ 63 severe fatigue
Number of patients with fatigue without hypogammaglobulinemia
Time frame: 1.5 years
The primary endpoint will be measured as frequency (%) of fatigue (defined as Fatigue Scala for Motor and Cognitive Function (FSMC) total ≥ 43 points) in MS patients with IgG-deficiency (IgG serum concentration <7.0 g/L) compared to those with normal IgG-serum concentration (≥ 7.0 g/L). The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue) FSMC Sum Score: ≥ 43 points mild fatigue, ≥ 53 points moderate fatigue, ≥ 63 severe fatigue
1 secondary outcome
Fatigue and infections
Time frame: 1.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lara Diem, MD principal investigator
Inselspital University Hospital of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypogammaglobulinemia and Multiple Sclerosis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lara Diem, MD (0041316327000, larafrancesca.diem@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with fatigue and hypogammaglobulinemia (time frame: 1.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.