Natural History of Pompe Disease

NCT ID: NCT03564561

Last Updated: 2024-04-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-06-07
• Study Completion Date: 2033-03-31

Brief Summary

The project is a prospective study in which patients affected by adult-onset Pompe disease with c.-32-13T>G mutation in the GAA gene will be followed-up during two years to describe the natural history using clinical, imaging, histological and molecular parameters.

Secondary objectives are:

• To identify biomarkers for assessing efficacy of future therapies based on correcting aberrant alternative splicing in Pompe patients with c.-32-13T>G mutations.
• To determine effectiveness of antisense oligonucleotide chemistries to restore full length GAA transcripts, GAA protein and GAA enzyme activity in fibroblasts and myoblasts obtained from skin and muscle biopsies as well as leucocytes of Pompe patients with c.-32-13T>G mutations.

Detailed Description

Study aim:

The principal objective of the study is to find biomarkers and clinical criteria that correlate with the disease progression.

Methods:

Clinical information will be obtained according to a pre-defined protocol including six visits: screening visit, visit at baseline, visits at 6 months, 12 months, 18 months and 24 months.

At visits following tests will be performed:

Respiratory assessment (including clinical assessment using the Borg scale, identification of clinical signs of alveolar hypoventilation, documentation of the daily duration on and off mechanical ventilation, spirometry, determination of lung volumes and slow vital capacity, peak cough flow, blood gazes, measurement of maximal inspiratory and expiratory pressures during the Müller maneuver, sniff nasal inspiratory pressure, mouth inspiratory pressure, twitch mouth pressure, esophageal and transdiaphragmatic pressures during voluntary respiration and following magnetic stimulation of diaphragmatic nerves, optoelectronic measurement of abdominal contribution to vital capacity, inspiratory capacity and tidal volume, measure of diaphragm mobility using ultrasound, sleep studies using polysomnography for non-ventilated patients and oximetry for patients using non-invasive mechanical ventilation, coupled with ECG recording).

Motor assessment (including the MFM motor function measure scale, timed 10 meters run/walk test, timed test for standing up from sitting positions, timed test for standing up from supine position, time taken to climb 4 stairs, 6-minute walk test, three-dimensional analysis of walk, quadriceps muscle strength assessed following magnetic stimulation of femoral nerve, EMG).

Assessment of body composition (including determination of lean mass, body mass index and bone mineral density by dual X-ray absorptiometry).

Assessment of skeletal muscle structure using whole body magnetic resonance imaging.

Assessment of heart function using heart echography and ECG. Assessment of live quality (including "Rotterdam handicap scale", "Rasch-built Pompe-specific Activity (R-Pact) scale " and EQ5D-5L questionnaires).

Biomaterial collection of biomarker analysis (including dosing serum CPK, GPT and GOT, GAA mutational analysis of both alleles, biobanking of serum, DNA and urine, muscle biopsy for histological analysis, quantification of exon 2 alternative splicing and residual GAA enzyme activity, myoblast culture for quantification of alternative splicing and residual GAA enzyme activity, muscle biopsy and myoblast culture biobanking, skin biopsy for quantification of alternative splicing and residual GAA enzyme activity, fibroblast cultures for quantification of alternative splicing and residual GAA enzyme activity, biobanking of fibroblasts).

In vitro treatment of myoblasts and fibroblasts with antisense oligonucleotide chemistries and quantification of restoration of normal splicing, GAA protein and GAA enzyme activity.

All data collect will be introduced in a database and afterwards statistically analyzed.

Expected results:

To determine exact natural history of Pompe disease, to identify biomarkers useful to follow-up the progression of Pompe disease and for quantifying therapy effects of future therapies that aim at restoring a normal splicing in patients with c.-32-13T>G mutations.

Funding:

This project is funded by the French Agence National de la Recherche, the French Direction Générale de l'Offre de Soins and the Acid Maltase Deficiency Association.

Conditions

Glycogen Storage Disease Type II, Adult

Study Design

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

Eligibility Criteria

Inclusion Criteria

• Pompe disease Patient with c.-32-13T>G mutation in at least one allele of GAA gene.
• Ambulating patient : six-minute walk test distance > 50 m.
• Patient aged between 18 and 80 years.
• Informed consent signed par patient.
• Patient covered by a health insurance.

Exclusion Criteria

• Invasive mechanical ventilation
• Pregnant woman
• Presence of comorbidity, in particular preexisting diseases like chronic infectious diseases (VIH infection, hepatitis or others), asthma, malignant tumour, hematologic diseases
• Patient who participate in another clinical trial
• Life expectancy < 12 months
• Unable to understand instructions and restraints of the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helge Amthor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Raymond Poincaré

Pascal Laforêt, MD, PhD

Role: STUDY_DIRECTOR

Hôpital Raymond Poincaré

Locations

Hôpital Raymond Poincaré

Garches, Hauts-de-Seine, France

Site Status: RECRUITING

Countries

France

Central Contacts

Helge Amthor, MD, PhD

Role: CONTACT

helge.amthor@aphp.fr

+ 33 1 47 10 78 90

Pascal Laforêt, MD, PhD

Role: CONTACT

pascal.laforet@aphp.fr

+ 33 1 47 10 37 76

Other Identifiers

2017-A02458-45

Identifier Type: REGISTRY

Identifier Source: secondary_id

P160405J

Identifier Type: -

Identifier Source: org_study_id