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Trial record 48 of 103 for:    Pompe Disease

Natural History of Pompe Disease (POMPE)

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ClinicalTrials.gov Identifier: NCT03564561
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease
Glycogen Storage Disease Type II, Adult

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical and Molecular Aspects of Adult Onset Pompe Disease: a Natural History Study
Actual Study Start Date : June 7, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021





Primary Outcome Measures :
  1. The Six-Minute Walk Test [ Time Frame: At baseline ]
  2. The Six-Minute Walk Test [ Time Frame: at 6 months ]
  3. The Six-Minute Walk Test [ Time Frame: at 12 months ]
  4. The Six-Minute Walk Test [ Time Frame: at 18 months ]
  5. The Six-Minute Walk Test [ Time Frame: at 24 months ]

Secondary Outcome Measures :
  1. Moter assessment: quadriceps strength [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Quadriceps muscle strength assessed following magnetic stimulated of femoral nerve.

  2. Moter assessment: : the MFM moter function measure scale [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Measurement of motor function by MFM (Motor Function Measure) scale.

  3. Moter assessment: timed 10 meters run/walk test [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Time for a 10-meter walk.

  4. Moter assessment: timed test for standing up from sitting position [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Time for getting up from a chair.

  5. Moter assessment: timed test for standing up from supine position [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Time for getting up from decubitus position.

  6. Moter assessment: time taken to climb 4 stairs [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Time for climbing 4 stairs.

  7. Moter assessment: three-dimensional analysis of walk [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    3D analysis of walking.

  8. Moter assessment: 6-minute walk test [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    The 6-minute walk test.

  9. Body composition [ Time Frame: At baseline, 12th and 24th months ]
    Osteodensitometry.

  10. Body composition [ Time Frame: At baseline, 12th and 24th months ]
    Body composition (ratio lean mass / fat mass) measure by dual-energy X-ray absorptiometry.

  11. Body composition [ Time Frame: At baseline, 12th and 24th months ]
    Body Mass Index (BMI).

  12. Evaluation of skeletal muscle by MRI imaging [ Time Frame: At baseline, 12th and 24th months ]

    Whole-body muscle MRI protocol :

    • Short tau inversion recovery (STIR).
    • T2-axial and coronal 3D.
    • IDEAL IQ.

  13. Respiratory parameters: dyspnea using Borg scale [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Evaluation of dyspnea using Borg scale.

  14. Respiratory assessment: alveolar hypoventilation identification [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Identification of clinical signs of alveolar hypoventilation.

  15. Respiratory parameters: daily duration of non-ventilation for ventilated patients [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Daily duration of non-ventilation for ventilated patients.

  16. Heart function assessment [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Assessment of heart assessment using heart echography

  17. Heart function assessment [ Time Frame: At baseline, at 6, 12, 18 and 24 months ]
    Assessment of heart assessment using ECG

  18. Quality of life assessment [ Time Frame: At baseline ]
    Evaluate by Questionnaire EQ5D-5L.

  19. Quality of life assessment [ Time Frame: At baseline ]
    Evaluate by Rotterdam handicap scale.

  20. Quality of life assessment [ Time Frame: At baseline ]
    Evaluate by Rasch-built Pompe-specific activity (R-Pact) scale.

  21. Histological features [ Time Frame: At baseline ]
    Histological study by using muscular biopsy culture with Periodic acid-Schiff stain and H&E stain.

  22. Genotype [ Time Frame: At baseline ]
    Determination of patient's GAA genotypes on blood sample.

  23. Molecular and biochemical parameters: muscular biopsy [ Time Frame: At baseline ]

    Muscular biopsy:

    Quantification of alternative splicing and residual enzymatic activity of acid alpha-glucosidase (GAA) of Pompe patient with c.-32 -13T>G mutation of GAA gene.


  24. Molecular and biochemical parameters: cutaneous biopsy [ Time Frame: At baseline ]

    Cutaneous biopsy:

    Quantification of alternative splicing and residual enzymatic activity of acid alpha-glucosidase (GAA) of Pompe patient with c.-32 -13T>G mutation of GAA gene.


  25. Biomarkers [ Time Frame: At baseline ]

    Blood sample (serum):

    Dosing of CPK, GPT and GOT level in serum.



Biospecimen Retention:   Samples With DNA

Blood, urine, skeletal muscle biopsy, skin biopsy:

  1. Blood for serum markers, DNA and white blood cell culture (lymphoblastoid cell line).
  2. Skeletal muscle biopsy for histology, RNA and protein analysis, myoblast culture.
  3. Skin biopsy for RNA and protein analysis, fibroblast culture.
  4. Urine for biomarker analysis.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03564561


Contacts
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Contact: Helge Amthor, MD, PhD + 33 1 47 10 78 90 helge.amthor@aphp.fr
Contact: Pascal Laforêt, MD, PhD + 33 1 47 10 37 76 pascal.laforet@aphp.fr

Locations
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France
Hôpital Raymond Poincaré Recruiting
Garches, Hauts-de-Seine, France, 92380
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Helge Amthor, MD, PhD Hôpital Raymond Poincaré
Study Director: Pascal Laforêt, MD, PhD Hôpital Raymond Poincaré

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03564561     History of Changes
Other Study ID Numbers: P160405J
2017-A02458-45 ( Registry Identifier: N° ID RCB )
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
glycogen storage disease type II, adult
Pompe disease
clinical evolution
molecular evolution
follow-up
c.-32-13T>G mutation
antisense oligonucleotide treatment
in vitro

Additional relevant MeSH terms:
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Glycogen Storage Disease Type II
Glycogen Storage Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors