Enzyme Replacement Therapy in Pompe DiseaseNCT03147664
Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease
An observational study of Enzyme Replacement Therapy in Pompe Disease, run by Rambam Health Care Campus.
Trial summary
Introduction: Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric Pompe patients. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Enzyme Replacement Therapy in Pompe Disease
- Type of treatment
- Injection or infusion
- How many people
- 5 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2014to 30 Mar 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Pediatric Pompe patients diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene. Age ≥8 y/o, ERT ≥1 year, capable of cycling on a stationary bicycle.
Who may be able to join
- Pompe disease diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene
- Age ≥8 y/o
- ERT ≥1 year
- Capable of cycling on a stationary bicycle.
Who cannot join
- Invasive ventilation
- Continuous ventilation and/or continuous oxygen supplementation to maintain oxygen saturation >90%
- Acute illness on visit day or one day prior.
About this study
Introduction: Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric Pompe patients.
Methods: Pompe patients (10-19 years) were evaluated before and two days after ERT using cardiopulmonary exercise testing (CPET), six minutes walking test (6MWT) and motor function test (GMFM-88).
Read the detailed description
Pompe disease is an inherited autosomal recessive glycogen storage disease caused by partial or total deficiency of acid α-glucosidase (GAA), resulting in the accumulation of glycogen in the lysosomes of skeletal muscles, heart, liver and other tissues. There is an inverse correlation between the amount of residual GAA activity and disease severity. The clinical phenotype varies with regard to age of onset, organ involvement, and severity of progression. In 2006, enzyme replacement therapy (ERT) with recombinant human GAA (Genzyme Corporation, Cambridge MA, USA) was approved and, since then, decisive modification of the course of the disease has been reported. Clinical studies in infants showed that ERT led to improvement in cardiac, respiratory and skeletal muscle functions, with achievement of independent walking, higher levels of physical activity, and survival beyond infancy.
Exercise capacity significantly affects Pompe patients' clinical picture and quality of life [5]. However, data on the effects of ERT on physiological variables related to exercise capacity is scarce. Cardiopulmonary exercise testing (CPET) is a well-known procedure to assess exercise capacity in adults and children in healthy and chronic conditions. Little is known regarding exercise capacity in the pediatric Pompe population. Our aim was to evaluate the acute effect of ERT on exercise capacity and different physiological variables in pediatric Pompe patients.
Patients were evaluated before and two days after ERT (20mg/kg/EOW). Each evaluation included CPET, pulmonary function tests, 6MWT and GMFM-88. All tests were carried out by the same experienced physician, exercise physiologist, and physiotherapist.
Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT.
Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed.
- Keywords
- pompe disease, exercise capacity, cardiopulmonary exercise testing
- Medical subject headings
- Glycogen Storage Disease Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pediatric Pompe patients | Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT. Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in oxygen Uptake
Change in mount of oxygen consumed per amount of time measured during 15 minutes of an exercise test.
Measured: 3 days
Secondary outcomes (3)
6 Minute walk test
The distance an individual walked in 6 minutes.
Measured: 3 days
Gross motor function measure score sheet (GMFM-88)
The patient is evaluated in the active performance of 88 physical tasks and the scoring range for each task ranges from 0=does not initiate, 1=initiates, 2=partially completes, 3=completes, NT=not tested. The total score is the sum of all tasks divided to the maximal potential score in percentage. Evaluation time ~ 30 minutes.
Measured: 3 days
Spirometry
Pulmonary function as assessed by spirometry. Evaluation time - 5 minutes.
Measured: 3 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2017
- Study start1 Jan 2014
- Primary completion30 Apr 2014
- Study completion30 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enzyme Replacement Therapy in Pompe DiseaseStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lea Bentur, Prof., Principal investigator, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03147664
- Sponsor's protocol ID
- 3190-RMB-CTIL
- Status last verified
- May 2017
- First submitted
- 30 Apr 2017
- Last updated
- 16 May 2017
- 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 16 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease
- ClinicalTrials.gov ID
- NCT03147664
- Acronym / sponsor ID
- 3190-RMB-CTIL
- Keywords
- pompe disease, exercise capacity, cardiopulmonary exercise testing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Study start
- 1 Jan 2014 (actual)
- Primary completion
- 30 Apr 2014 (actual)
- Study completion
- 30 Mar 2017 (actual)
- First posted
- 10 May 2017 (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.
Introduction: Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric Pompe patients.
Methods: Pompe patients (10-19 years) were evaluated before and two days after ERT using cardiopulmonary exercise testing (CPET), six minutes walking test (6MWT) and motor function test (GMFM-88).
Detailed description
Pompe disease is an inherited autosomal recessive glycogen storage disease caused by partial or total deficiency of acid α-glucosidase (GAA), resulting in the accumulation of glycogen in the lysosomes of skeletal muscles, heart, liver and other tissues. There is an inverse correlation between the amount of residual GAA activity and disease severity. The clinical phenotype varies with regard to age of onset, organ involvement, and severity of progression. In 2006, enzyme replacement therapy (ERT) with recombinant human GAA (Genzyme Corporation, Cambridge MA, USA) was approved and, since then, decisive modification of the course of the disease has been reported. Clinical studies in infants showed that ERT led to improvement in cardiac, respiratory and skeletal muscle functions, with achievement of independent walking, higher levels of physical activity, and survival beyond infancy.
Exercise capacity significantly affects Pompe patients' clinical picture and quality of life [5]. However, data on the effects of ERT on physiological variables related to exercise capacity is scarce. Cardiopulmonary exercise testing (CPET) is a well-known procedure to assess exercise capacity in adults and children in healthy and chronic conditions. Little is known regarding exercise capacity in the pediatric Pompe population. Our aim was to evaluate the acute effect of ERT on exercise capacity and different physiological variables in pediatric Pompe patients.
Patients were evaluated before and two days after ERT (20mg/kg/EOW). Each evaluation included CPET, pulmonary function tests, 6MWT and GMFM-88. All tests were carried out by the same experienced physician, exercise physiologist, and physiotherapist.
Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT.
Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pediatric Pompe patients | – | –Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT. Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed. |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Pediatric Pompe patients diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene. Age ≥8 y/o, ERT ≥1 year, capable of cycling on a stationary bicycle.
Key inclusion criteria (4 listed)
- Pompe disease diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene
- Age ≥8 y/o
- ERT ≥1 year
- Capable of cycling on a stationary bicycle.
Key exclusion criteria (3 listed)
- Invasive ventilation
- Continuous ventilation and/or continuous oxygen supplementation to maintain oxygen saturation >90%
- Acute illness on visit day or one day prior.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in oxygen Uptake
Time frame: 3 days
Change in mount of oxygen consumed per amount of time measured during 15 minutes of an exercise test.
3 secondary outcomes
6 Minute walk test
Time frame: 3 days
Gross motor function measure score sheet (GMFM-88)
Time frame: 3 days
Spirometry
Time frame: 3 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2017.
- Individual participant dataSharing planned: No
Related trials for Enzyme Replacement Therapy in Pompe Disease
Not yet recruitingPhase 2
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RecruitingPhase 1
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of DNL952 in Adult Participants With Late-Onset Pompe Disease
Late-onset Pompe Disease
RecruitingPhase 2
Study of S-606001 as an Add-on to Enzyme Replacement Therapy (ERT) in Participants With Late-onset Pompe Disease (LOPD)
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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. This study is not recruiting at the moment.
Lea Bentur, Prof. principal investigator
Rambam Health Care Campus
Questions about this trial
What is this clinical trial studying?
An observational study of Enzyme Replacement Therapy in Pompe Disease, run by Rambam Health Care Campus.
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 4 inclusion and 3 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: finished, as of the sponsor's last update on 16 May 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in oxygen Uptake (time frame: 3 days). 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 16 May 2017.