X-linked Moesin Associated Immunodeficiency

Autoimmune Diseases Clinical Trial

— X-MAIDReg  

Official title:

Etude Multicentrique Internationale rétrospective Des Patients Atteints de déficit Immunitaire associé à la moésine lié au Chromosome X (X Maid Pour X-linked Moesin Associated Immunodeficiency)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06278337
• Other study ID #: C19-35
• Status: Recruiting
• Start date: August 12, 2021
• Est. completion date: January 12, 2027

Study information

• Verified date: January 2024
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Isabelle ANDRE, Doctor
• Phone: 01 42 75 43 37
• Email: isabelle.andre[@]inserm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Moesin deficiency was initially described in 7 male participants aged 4 to 69 years and is characterized by lymphopenia of the 3 lineages and moderate neutropenia. Genetically, 6 out of 7 participants had the same missense mutation in the moesin gene located on the X chromosome. The 7th patient has a mutation leading to the premature introduction of a STOP codon into the protein.Clinically the 7 participants with X-linked moesin-associated immunodeficiency all presented with recurrent bacterial infections of the respiratory, gastrointestinal or urinary tracts, and some had severe varicella.Therapeutically, in the absence of a molecular diagnosis and due to his SCID-like phenotype, one patient was treated with geno-identical hematopoietic stem cell transplantation . The remaining are untreated or treated with immunoglobulin substitution and/or prophylactic antibiotics. Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The Investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigator propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each patient according to his or her clinical picture

Description:

Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigators propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each participant according to his or her clinical picture

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: January 12, 2027
• Est. primary completion date: August 12, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male patient with a mutation in the MOESIN gene (MSN)
• No objection to the collection of personal health data Exclusion Criteria: -

Related Conditions & MeSH terms

• Autoimmune Diseases
• Diagnosis
• Immune Deficiency
• Immunologic Deficiency Syndromes
• Infections

Intervention

Genetic:
• genetic restrospective study
it is not an interventional study but observational

Locations

Country	Name	City	State
Australia	Genomic Research Centre, School of Biomedical Sciences Institute of Health and Biomedical Innovation	Brisbane
Belgium	Hôpital Universitaire de la Reine Fabiola	Bruxelles
France	Hôpital Necker	Paris
France	CHU Rennes, CNRS UMR 629	Rennes
France	CHU St Etienne Hôpital Nord	Saint-Étienne
Japan	Tokyo Medical and Dental University (TMDU)	Bunkyo-Ku
Netherlands	Departments of Internal Medicine and Immunology	Rotterdam
United States	National Institutes of Health	Bethesda	Maryland
United States	Perelman School of medecine	Philadelphia	Pennsylvania
United States	Brown University	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Japan,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	secondary objectives 2	What is the state of their immune system and, depending on this state, the CID or SCID classification of the disease.	through study completion, and average 3 years
Other	secondary objective 3	What are the clinical manifestations of the disease (cutaneous, infectious, autoimmune)?	All the patients are male. As a result of their immune deficiency, patients suffer from recurrent bacterial infections of the respiratory, digestive and urinary tracts, as well as, in some cases, skin manifestations such as eczema, alopecia and molluscum
Other	secondary objectives 4	What impact does the disease have on their development?	Among patients diagnosed in the first years of life, none showed developmental defects.
Other	secondary objective 5	What are the treatments and their consequences?	Treatments range from no prophylaxis at all to antibiotic prophylaxis, with or without immunoglobulin therapy, granulocyte-colony-stimulating factor therapy or hematopoietic stem cell allograft.
Primary	The main objective	The main objective is to study the clinical results of the different therapeutic options applied to X-MAID patients, and to investigate whether there is a correlation between treatment responses and mutation position	through study completion, and average 3 years
Secondary	Secondary objectives1	Circumstances of genetic diagnosis: at what age are these patients diagnosed, and by what means? (role of prenatal screening).	through study completion, and average 3 years