Ignite Creation Date:
2025-12-24 @ 12:21 PM
Ignite Modification Date:
2025-12-27 @ 10:08 PM
Study NCT ID:
NCT03564561
Status:
RECRUITING
Last Update Posted:
2024-04-08
First Post:
2018-03-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Natural History of Pompe Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006009', 'term': 'Glycogen Storage Disease Type II'}], 'ancestors': [{'id': 'D020140', 'term': 'Lysosomal Storage Diseases, Nervous System'}, {'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006008', 'term': 'Glycogen Storage Disease'}, {'id': 'D002239', 'term': 'Carbohydrate Metabolism, Inborn Errors'}, {'id': 'D016464', 'term': 'Lysosomal Storage Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood, urine, skeletal muscle biopsy, skin biopsy:\n\n1. Blood for serum markers, DNA and white blood cell culture (lymphoblastoid cell line).\n2. Skeletal muscle biopsy for histology, RNA and protein analysis, myoblast culture.\n3. Skin biopsy for RNA and protein analysis, fibroblast culture.\n4. Urine for biomarker analysis.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-06-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2033-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-05', 'studyFirstSubmitDate': '2018-03-27', 'studyFirstSubmitQcDate': '2018-06-10', 'lastUpdatePostDateStruct': {'date': '2024-04-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-06-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2033-03', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The Six-Minute Walk Test', 'timeFrame': 'At baseline'}, {'measure': 'The Six-Minute Walk Test', 'timeFrame': 'at 6 months'}, {'measure': 'The Six-Minute Walk Test', 'timeFrame': 'at 12 months'}, {'measure': 'The Six-Minute Walk Test', 'timeFrame': 'at 18 months'}, {'measure': 'The Six-Minute Walk Test', 'timeFrame': 'at 24 months'}], 'secondaryOutcomes': [{'measure': 'Moter assessment: quadriceps strength', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Quadriceps muscle strength assessed following magnetic stimulated of femoral nerve.'}, {'measure': 'Moter assessment: : the MFM moter function measure scale', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Measurement of motor function by MFM (Motor Function Measure) scale.'}, {'measure': 'Moter assessment: timed 10 meters run/walk test', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Time for a 10-meter walk.'}, {'measure': 'Moter assessment: timed test for standing up from sitting position', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Time for getting up from a chair.'}, {'measure': 'Moter assessment: timed test for standing up from supine position', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Time for getting up from decubitus position.'}, {'measure': 'Moter assessment: time taken to climb 4 stairs', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Time for climbing 4 stairs.'}, {'measure': 'Moter assessment: three-dimensional analysis of walk', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': '3D analysis of walking.'}, {'measure': 'Moter assessment: 6-minute walk test', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'The 6-minute walk test.'}, {'measure': 'Body composition', 'timeFrame': 'At baseline, 12th and 24th months', 'description': 'Osteodensitometry.'}, {'measure': 'Body composition', 'timeFrame': 'At baseline, 12th and 24th months', 'description': 'Body composition (ratio lean mass / fat mass) measure by dual-energy X-ray absorptiometry.'}, {'measure': 'Body composition', 'timeFrame': 'At baseline, 12th and 24th months', 'description': 'Body Mass Index (BMI).'}, {'measure': 'Evaluation of skeletal muscle by MRI imaging', 'timeFrame': 'At baseline, 12th and 24th months', 'description': 'Whole-body muscle MRI protocol :\n\n* Short tau inversion recovery (STIR).\n* T2-axial and coronal 3D.\n* IDEAL IQ.'}, {'measure': 'Respiratory parameters: dyspnea using Borg scale', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Evaluation of dyspnea using Borg scale.'}, {'measure': 'Respiratory assessment: alveolar hypoventilation identification', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Identification of clinical signs of alveolar hypoventilation.'}, {'measure': 'Respiratory parameters: daily duration of non-ventilation for ventilated patients', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Daily duration of non-ventilation for ventilated patients.'}, {'measure': 'Heart function assessment', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Assessment of heart assessment using heart echography'}, {'measure': 'Heart function assessment', 'timeFrame': 'At baseline, at 6, 12, 18 and 24 months', 'description': 'Assessment of heart assessment using ECG'}, {'measure': 'Quality of life assessment', 'timeFrame': 'At baseline', 'description': 'Evaluate by Questionnaire EQ5D-5L.'}, {'measure': 'Quality of life assessment', 'timeFrame': 'At baseline', 'description': 'Evaluate by Rotterdam handicap scale.'}, {'measure': 'Quality of life assessment', 'timeFrame': 'At baseline', 'description': 'Evaluate by Rasch-built Pompe-specific activity (R-Pact) scale.'}, {'measure': 'Histological features', 'timeFrame': 'At baseline', 'description': 'Histological study by using muscular biopsy culture with Periodic acid-Schiff stain and H\\&E stain.'}, {'measure': 'Genotype', 'timeFrame': 'At baseline', 'description': "Determination of patient's GAA genotypes on blood sample."}, {'measure': 'Molecular and biochemical parameters: muscular biopsy', 'timeFrame': 'At baseline', 'description': 'Muscular biopsy:\n\nQuantification of alternative splicing and residual enzymatic activity of acid alpha-glucosidase (GAA) of Pompe patient with c.-32 -13T\\>G mutation of GAA gene.'}, {'measure': 'Molecular and biochemical parameters: cutaneous biopsy', 'timeFrame': 'At baseline', 'description': 'Cutaneous biopsy:\n\nQuantification of alternative splicing and residual enzymatic activity of acid alpha-glucosidase (GAA) of Pompe patient with c.-32 -13T\\>G mutation of GAA gene.'}, {'measure': 'Biomarkers', 'timeFrame': 'At baseline', 'description': 'Blood sample (serum):\n\nDosing of CPK, GPT and GOT level in serum.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['glycogen storage disease type II, adult', 'Pompe disease', 'clinical evolution', 'molecular evolution', 'follow-up', 'c.-32-13T>G mutation', 'antisense oligonucleotide treatment', 'in vitro'], 'conditions': ['Glycogen Storage Disease Type II, Adult']}, 'descriptionModule': {'briefSummary': '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.\n\nSecondary objectives are:\n\n* To identify biomarkers for assessing efficacy of future therapies based on correcting aberrant alternative splicing in Pompe patients with c.-32-13T\\>G mutations.\n* 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.', 'detailedDescription': 'Study aim:\n\nThe principal objective of the study is to find biomarkers and clinical criteria that correlate with the disease progression.\n\nMethods:\n\nClinical 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.\n\nAt visits following tests will be performed:\n\nRespiratory 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).\n\nMotor 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).\n\nAssessment of body composition (including determination of lean mass, body mass index and bone mineral density by dual X-ray absorptiometry).\n\nAssessment of skeletal muscle structure using whole body magnetic resonance imaging.\n\nAssessment 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).\n\nBiomaterial 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).\n\nIn vitro treatment of myoblasts and fibroblasts with antisense oligonucleotide chemistries and quantification of restoration of normal splicing, GAA protein and GAA enzyme activity.\n\nAll data collect will be introduced in a database and afterwards statistically analyzed.\n\nExpected results:\n\nTo 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.\n\nFunding:\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adult patients between 18 and 80 years with adult-onset Pompe disease who carry the common c.-32-13T\\>G mutation of GAA gene, treated or not by Myozyme.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Pompe disease Patient with c.-32-13T\\>G mutation in at least one allele of GAA gene.\n* Ambulating patient : six-minute walk test distance \\> 50 m.\n* Patient aged between 18 and 80 years.\n* Informed consent signed par patient.\n* Patient covered by a health insurance.\n\nExclusion Criteria:\n\n* Invasive mechanical ventilation\n* Pregnant woman\n* Presence of comorbidity, in particular preexisting diseases like chronic infectious diseases (VIH infection, hepatitis or others), asthma, malignant tumour, hematologic diseases\n* Patient who participate in another clinical trial\n* Life expectancy \\< 12 months\n* Unable to understand instructions and restraints of the study'}, 'identificationModule': {'nctId': 'NCT03564561', 'acronym': 'POMPE', 'briefTitle': 'Natural History of Pompe Disease', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Clinical and Molecular Aspects of Adult Onset Pompe Disease: a Natural History Study', 'orgStudyIdInfo': {'id': 'P160405J'}, 'secondaryIdInfos': [{'id': '2017-A02458-45', 'type': 'REGISTRY', 'domain': 'N° ID RCB'}]}, 'contactsLocationsModule': {'locations': [{'zip': '92380', 'city': 'Garches', 'state': 'Hauts-de-Seine', 'status': 'RECRUITING', 'country': 'France', 'facility': 'Hôpital Raymond Poincaré', 'geoPoint': {'lat': 48.84226, 'lon': 2.18232}}], 'centralContacts': [{'name': 'Helge Amthor, MD, PhD', 'role': 'CONTACT', 'email': 'helge.amthor@aphp.fr', 'phone': '+ 33 1 47 10 78 90'}, {'name': 'Pascal Laforêt, MD, PhD', 'role': 'CONTACT', 'email': 'pascal.laforet@aphp.fr', 'phone': '+ 33 1 47 10 37 76'}], 'overallOfficials': [{'name': 'Helge Amthor, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hôpital Raymond Poincaré'}, {'name': 'Pascal Laforêt, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hôpital Raymond Poincaré'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}