MucopolysaccharidosesRespiGAGNCT04112602
Respiratory Cathepsins, Proteases Inhibitors and Glycosaminoglycans (GAG) in Mucopolysaccharidosis
An observational study of Mucopolysaccharidoses, run by University Hospital, Tours at 7 sites in France.
Trial summary
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results in cellular accumulation of GAGs fragments leading to progressive multi-system manifestations, with respiratory impairment. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Mucopolysaccharidoses
- What is being tested?
- Sputum and Tracheal aspiration
- How many people
- 27 participants
- Where
- 7 sitesFrance
- Study dates
- 12 Nov 2019to 26 Jun 2020
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Patients with MPS: In this cohort are included patients under 18 years old with MPS (all types). The objective is to be representative of the diversity of MPS, and of this evolution. Non-MPS patients: In this control group are included patients under 18 years old, with no respiratory problems, no MPS.
Who may be able to join
- Patient with a confirmed diagnosis (enzymatic activity, and/or genotyping) of MPS, all types (I, II, III, IV, VI, VII, IX)
- Aged from 0 to 17 years old
- Non inclusion Criteria:
- Chronic respiratory disease independent of MPS disease (potential interferences with our analyzes)
- Inability to obtain pulmonary samples
- Refusal of the patient, parent or legal representative to participate in this study
Show all 12Show fewer
- Patient with no respiratory disease
- Aged from 0 to 17 years old
- Non inclusion Criteria:
- Emergency medical situation
- Inability to obtain pulmonary expectoration
- Refusal of the patient, parent or legal representative to participate in this study
Who cannot join
- Impossibility to use pulmonary samples (insufficient volume, conservation problem, etc.)
- Non-MPS patients:
- Impossibility to use pulmonary samples (insufficient volume, conservation problem, etc.)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
Metabolic Disease Competence Centre - Medical Genetics Department - University Hospital, Angers
Angers
Metabolic Disease Reference Centre - Medical Genetics Department - University Hospital, Bordeaux
Bordeaux
Metabolic Disease Competence Centre - Medical Genetics Department - University Hospital, Brest
Brest
Metabolic Disease Competence Centre - Pediatrics Department - University Hospital, Rennes
Rennes
Metabolic Disease Reference Centre - Pediatrics Department - University Hospital, Toulouse
Toulouse
Metabolic Disease Reference Centre - Pediatrics Department - University Hospital, Tours
Tours
Pediatric Resuscitation Unit - Universty Hospital, Tours
Tours
About this study
Official title: Respiratory Impairment in Mucopolysaccharidosis Patients: Impact of Glycosaminoglycans (GAG) on the Proteases/Antiproteases Balance
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results in cellular accumulation of GAGs fragments leading to progressive multi-system manifestations, with respiratory impairment. The cellular and molecular mechanisms responsible for the pulmonary impairment remain largely unknown. Specific GAGs, such as those accumulating in MPS, may act as potent inhibitors of some respiratory enzymes, like lysosomal cathepsins, depending on the nature of GAGs and their concentration. It is well established that deregulation of cathepsins levels plays a major role in the pathophysiology of some chronic respiratory diseases, such as cystic fibrosis. The role of cathepsins and their inhibitors in respiratory samples of MPS patients has never been studied. This study will focus on the status/activity of these proteases and their endogenous inhibitors in the sputum or tracheal aspiration of patients with MPS. Our main hypothesis is that high levels of GAGs in MPS patients impair the physiological activity of cathepsins and their inhibitors.
Read the detailed description
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results in cellular accumulation of GAGs fragments leading to progressive multi-system manifestations (central nervous system involvement, dysmorphism, skeletal abnormalities, cardiomyopathy, ear/nose/throat and respiratory problems). Impairment of pulmonary function is an important health problem for patients with MPS.
Various therapeutic approaches have been developed to restore deficient enzymatic activity (stem cell transplantation, enzyme replacement therapy, gene therapy), but new therapeutic approaches may be required, in addition to these current conventional treatments. In particular, respiratory failure is not fully restored. The cellular and molecular mechanisms responsible for lung dysfunction remain today largely unknown and require additional investigations. It is well established that GAGs, upon specific conditions either stimulate or inhibit the activity of specific enzymes named cathepsins.
Cysteine cathepsins are lysosomal proteases that can be secreted extracellularly by macrophages, epithelial cells and fibroblasts. Imbalance between cathepsins and their inhibitors in favor to proteolysis has been demonstrated in patients with chronic pulmonary diseases (silicosis, cystic fibrosis). By contrast, high levels of their endogenous inhibitors are found in idiopathic fibrosis. Interestingly, previous studies reported that accumulation of sulphated GAGs (chondroitin sulfate, heparan sulfate, dermatan sulfate) impaired the collagenolytic activity of cathepsin K in a MPS I mouse model, supporting that cathepsin K participates to the pathophysiology of the bone involvement in patients with MPS. Moreover, other related cathepsins are regulated in vitro by GAGs.
Thus, inhibition of cathepsins may contribute to the respiratory impairment in MPS patients. However, their expression and their role in the airway of MPS patients are still unknown. Moreover, little is known on GAG levels in MPS lungs. The main hypothesis of the proposed research is to evaluate the levels of sulfated GAGs (heparan sulfate, chondroitin sulfate, dermatan sulfate) in respiratory samples of MPS patients and the ability of theses GAGs to modulate the proteolytic activities of lysosomal cathepsins. This would lead to an abnormal remodeling of the extracellular matrix architecture, contributing to the respiratory disorders of patients with MPS. To validate this hypothesis, a correlational study will be performed to find a relationship between cathepsins expression/activity, GAGs concentrations and respiratory function.
This is a multicentre, prospective, non-interventional and case-control study (patients with MPS vs non-MPS patients). Pulmonary samples (biological waste) will be collected in patients after either a respiratory physiotherapy session (scheduled for routine care) or by tracheal aspiration when patients are intubated (intubation for imaging or surgery under general anesthesia). Collected samples will be used to assess the level of expression and activity of cathepsins and their inhibitors and the amount of sulfated GAGs.
Patients with MPS will be recruited in some Reference and Competence Centers for Metabolic Diseases in France (Angers, Bordeaux, Brest, Rennes, Toulouse, Tours). The non-MPS patients will be recruited at the Tours University Hospital (Pediatric Resuscitation).
Some medical data of patients with MPS will be collected retrospectively from the medical record. These data will be age, sex, type of MPS, respiratory assessment.
The data collected for the non-MPS patients will be age and sex.
The expected benefits are:
- Better understanding of the respiratory pathophysiology in MPS patients: by understanding the molecular cathepsins/GAGs interactions.
- Development of new therapeutic approaches for respiratory disease in patients with MPS: If we can prove that there is a dysregulation of pulmonary cathepsin activity in patients with MPS, a treatment that will restore this activity would be of great interest. This type of treatment is already studied in bone diseases such as osteoporosis. This treatment would be complementary to current conventional therapies, like stem cell transplant or enzyme replacement therapy.
- New therapeutic approaches potentially effective for other problems in patients with MPS:
The mechanism of cathepsin activity inhibition by GAGs is probably not lung-specific. GAGs accumulation and cathepsin expression are ubiquitous in humans. The role of cathepsins dysregulation by GAGs has already been described to explain some bone or cardiac involvements. These new therapeutic approaches could therefore also have a beneficial effect on other organs involvement in patients with MPS.
- Conditions
- Mucopolysaccharidoses
- Being tested
- Sputum, Tracheal aspiration
- Keywords
- mucopolysaccharidosis, lung cathepsins, proteases inhibitors, glycosaminoglycans
- Medical subject headings
- Mucopolysaccharidoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SputumOther
Sputum will be collected after a respiratory physiotherapy session, scheduled as part of routine care.
Tracheal aspirationOther
Tracheal aspirations will be collected in intubated patients (intubation for surgery under general anesthesia).
| Study group | Role | What they receive |
|---|---|---|
| Patients with MPS | In this cohort are included patients under 18 years old with MPS (all types). The objective is to be representative of the diversity of MPS, and of this evolution. Receives: Other: Sputum; Other: Tracheal aspiration | |
| Non-MPS patients | In this control group are included patients under 18 years old, with no respiratory problems, no MPS. Receives: Other: Tracheal aspiration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the expression of pulmonary cathepsins, proteases inhibitors and GAGs in MPS patients.
Detection and identification by Western blot. Results will be compared to non-MPS patients.
Measured: Day 1
Quantification of pulmonary cathepsins, protease inhibitors and GAGs in MPS patients.
Quantification by kinetics and ELISA assays. Results will be compared to non-MPS patients.
Measured: Day 1
Secondary outcomes (1)
Pulmonary cathepsins enzymatic activity measurement.
Enzyme activity measurement by enzymatic kinetics techniques.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start12 Nov 2019
- Primary completion26 Jun 2020
- Study completion26 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for MucopolysaccharidosesStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François Labarthe, MD-PhD, Study director, University Hospital, Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112602
- Sponsor's protocol ID
- RIPH3-RNI19/RespiGAG
- Other IDs
- 2019-A01361-56, 19.05.17.43323 RIPH 3 HPS
- Acronym
- RespiGAG
- Status last verified
- Jan 2022
- First submitted
- 1 Oct 2019
- Last updated
- 4 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S. Epidemiology of mucopolysaccharidoses. Mol Genet Metab. 2017 Jul;121(3):227-240. doi: 10.1016/j.ymgme.2017.05.016. Epub 2017 May 26.
PubMed 28595941Rapoport DM, Mitchell JJ. Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses. Mol Genet Metab. 2017 Dec;122S:49-54. doi: 10.1016/j.ymgme.2017.08.008. Epub 2017 Aug 25.
PubMed 28964643Kobayashi H. Recent trends in mucopolysaccharidosis research. J Hum Genet. 2019 Feb;64(2):127-137. doi: 10.1038/s10038-018-0534-8. Epub 2018 Nov 19.
PubMed 30451936Wilson S, Hashamiyan S, Clarke L, Saftig P, Mort J, Dejica VM, Bromme D. Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities. Am J Pathol. 2009 Nov;175(5):2053-62. doi: 10.2353/ajpath.2009.090211. Epub 2009 Oct 15.
PubMed 19834056Lalmanach G, Saidi A, Marchand-Adam S, Lecaille F, Kasabova M. Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases. Biol Chem. 2015 Feb;396(2):111-30. doi: 10.1515/hsz-2014-0210.
PubMed 25178906Bromme D, Lecaille F. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opin Investig Drugs. 2009 May;18(5):585-600. doi: 10.1517/13543780902832661.
PubMed 19388876Baldo G, Tavares AM, Gonzalez E, Poletto E, Mayer FQ, Matte UD, Giugliani R. Progressive heart disease in mucopolysaccharidosis type I mice may be mediated by increased cathepsin B activity. Cardiovasc Pathol. 2017 Mar-Apr;27:45-50. doi: 10.1016/j.carpath.2017.01.001. Epub 2017 Jan 6.
PubMed 28104572Sage J, Mallevre F, Barbarin-Costes F, Samsonov SA, Gehrcke JP, Pisabarro MT, Perrier E, Schnebert S, Roget A, Livache T, Nizard C, Lalmanach G, Lecaille F. Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity. Biochemistry. 2013 Sep 17;52(37):6487-98. doi: 10.1021/bi400925g. Epub 2013 Sep 4.
PubMed 23968158Kubaski F, Tomatsu S, Patel P, Shimada T, Xie L, Yasuda E, Mason R, Mackenzie WG, Theroux M, Bober MB, Oldham HM, Orii T, Shaffer TH. Non-invasive pulmonary function test on Morquio patients. Mol Genet Metab. 2015 Aug;115(4):186-92. doi: 10.1016/j.ymgme.2015.06.007. Epub 2015 Jun 23.
PubMed 26116954
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Respiratory Impairment in Mucopolysaccharidosis Patients: Impact of Glycosaminoglycans (GAG) on the Proteases/Antiproteases Balance
- ClinicalTrials.gov ID
- NCT04112602
- Acronym / sponsor ID
- RespiGAG / RIPH3-RNI19/RespiGAG
- Conditions
- Mucopolysaccharidoses
- Keywords
- mucopolysaccharidosis, lung cathepsins, proteases inhibitors, glycosaminoglycans
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 12 Nov 2019 (actual)
- Primary completion
- 26 Jun 2020 (actual)
- Study completion
- 26 Jun 2020 (actual)
- First posted
- 2 Oct 2019 (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.
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results in cellular accumulation of GAGs fragments leading to progressive multi-system manifestations, with respiratory impairment. The cellular and molecular mechanisms responsible for the pulmonary impairment remain largely unknown. Specific GAGs, such as those accumulating in MPS, may act as potent inhibitors of some respiratory enzymes, like lysosomal cathepsins, depending on the nature of GAGs and their concentration. It is well established that deregulation of cathepsins levels plays a major role in the pathophysiology of some chronic respiratory diseases, such as cystic fibrosis. The role of cathepsins and their inhibitors in respiratory samples of MPS patients has never been studied. This study will focus on the status/activity of these proteases and their endogenous inhibitors in the sputum or tracheal aspiration of patients with MPS. Our main hypothesis is that high levels of GAGs in MPS patients impair the physiological activity of cathepsins and their inhibitors.
Detailed description
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results in cellular accumulation of GAGs fragments leading to progressive multi-system manifestations (central nervous system involvement, dysmorphism, skeletal abnormalities, cardiomyopathy, ear/nose/throat and respiratory problems). Impairment of pulmonary function is an important health problem for patients with MPS.
Various therapeutic approaches have been developed to restore deficient enzymatic activity (stem cell transplantation, enzyme replacement therapy, gene therapy), but new therapeutic approaches may be required, in addition to these current conventional treatments. In particular, respiratory failure is not fully restored. The cellular and molecular mechanisms responsible for lung dysfunction remain today largely unknown and require additional investigations. It is well established that GAGs, upon specific conditions either stimulate or inhibit the activity of specific enzymes named cathepsins.
Cysteine cathepsins are lysosomal proteases that can be secreted extracellularly by macrophages, epithelial cells and fibroblasts. Imbalance between cathepsins and their inhibitors in favor to proteolysis has been demonstrated in patients with chronic pulmonary diseases (silicosis, cystic fibrosis). By contrast, high levels of their endogenous inhibitors are found in idiopathic fibrosis. Interestingly, previous studies reported that accumulation of sulphated GAGs (chondroitin sulfate, heparan sulfate, dermatan sulfate) impaired the collagenolytic activity of cathepsin K in a MPS I mouse model, supporting that cathepsin K participates to the pathophysiology of the bone involvement in patients with MPS. Moreover, other related cathepsins are regulated in vitro by GAGs.
Thus, inhibition of cathepsins may contribute to the respiratory impairment in MPS patients. However, their expression and their role in the airway of MPS patients are still unknown. Moreover, little is known on GAG levels in MPS lungs. The main hypothesis of the proposed research is to evaluate the levels of sulfated GAGs (heparan sulfate, chondroitin sulfate, dermatan sulfate) in respiratory samples of MPS patients and the ability of theses GAGs to modulate the proteolytic activities of lysosomal cathepsins. This would lead to an abnormal remodeling of the extracellular matrix architecture, contributing to the respiratory disorders of patients with MPS. To validate this hypothesis, a correlational study will be performed to find a relationship between cathepsins expression/activity, GAGs concentrations and respiratory function.
This is a multicentre, prospective, non-interventional and case-control study (patients with MPS vs non-MPS patients). Pulmonary samples (biological waste) will be collected in patients after either a respiratory physiotherapy session (scheduled for routine care) or by tracheal aspiration when patients are intubated (intubation for imaging or surgery under general anesthesia). Collected samples will be used to assess the level of expression and activity of cathepsins and their inhibitors and the amount of sulfated GAGs.
Patients with MPS will be recruited in some Reference and Competence Centers for Metabolic Diseases in France (Angers, Bordeaux, Brest, Rennes, Toulouse, Tours). The non-MPS patients will be recruited at the Tours University Hospital (Pediatric Resuscitation).
Some medical data of patients with MPS will be collected retrospectively from the medical record. These data will be age, sex, type of MPS, respiratory assessment.
The data collected for the non-MPS patients will be age and sex.
The expected benefits are:
- Better understanding of the respiratory pathophysiology in MPS patients: by understanding the molecular cathepsins/GAGs interactions.
- Development of new therapeutic approaches for respiratory disease in patients with MPS: If we can prove that there is a dysregulation of pulmonary cathepsin activity in patients with MPS, a treatment that will restore this activity would be of great interest. This type of treatment is already studied in bone diseases such as osteoporosis. This treatment would be complementary to current conventional therapies, like stem cell transplant or enzyme replacement therapy.
- New therapeutic approaches potentially effective for other problems in patients with MPS:
The mechanism of cathepsin activity inhibition by GAGs is probably not lung-specific. GAGs accumulation and cathepsin expression are ubiquitous in humans. The role of cathepsins dysregulation by GAGs has already been described to explain some bone or cardiac involvements. These new therapeutic approaches could therefore also have a beneficial effect on other organs involvement in patients with MPS.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with MPS | – | Other: Sputum, Other: Tracheal aspirationIn this cohort are included patients under 18 years old with MPS (all types). The objective is to be representative of the diversity of MPS, and of this evolution. |
| Non-MPS patients | – | Other: Tracheal aspirationIn this control group are included patients under 18 years old, with no respiratory problems, no MPS. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Patients with MPS: In this cohort are included patients under 18 years old with MPS (all types). The objective is to be representative of the diversity of MPS, and of this evolution. Non-MPS patients: In this control group are included patients under 18 years old, with no respiratory problems, no MPS.
Key inclusion criteria (12 listed)
- Patient with a confirmed diagnosis (enzymatic activity, and/or genotyping) of MPS, all types (I, II, III, IV, VI, VII, IX)
- Aged from 0 to 17 years old
- Chronic respiratory disease independent of MPS disease (potential interferences with our analyzes)
- Inability to obtain pulmonary samples
- Refusal of the patient, parent or legal representative to participate in this study
Key exclusion criteria (3 listed)
- Impossibility to use pulmonary samples (insufficient volume, conservation problem, etc.)
- Impossibility to use pulmonary samples (insufficient volume, conservation problem, etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SputumSputum will be collected after a respiratory physiotherapy session, scheduled as part of routine care. | Other | Patients with MPS |
| Tracheal aspirationTracheal aspirations will be collected in intubated patients (intubation for surgery under general anesthesia). | Other | Non-MPS patients, Patients with MPS |
Primary outcome
Evaluation of the expression of pulmonary cathepsins, proteases inhibitors and GAGs in MPS patients.
Time frame: Day 1
Detection and identification by Western blot. Results will be compared to non-MPS patients.
Quantification of pulmonary cathepsins, protease inhibitors and GAGs in MPS patients.
Time frame: Day 1
Quantification by kinetics and ELISA assays. Results will be compared to non-MPS patients.
1 secondary outcome
Pulmonary cathepsins enzymatic activity measurement.
Time frame: Day 1
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 4 Jan 2022.
- Background: PubMed 28595941Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S. Epidemiology of mucopolysaccharidoses. Mol Genet Metab. 2017 Jul;121(3):227-240. doi: 10.1016/j.ymgme.2017.05.016. Epub 2017 May 26.
- Background: PubMed 28964643Rapoport DM, Mitchell JJ. Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses. Mol Genet Metab. 2017 Dec;122S:49-54. doi: 10.1016/j.ymgme.2017.08.008. Epub 2017 Aug 25.
- Background: PubMed 30451936Kobayashi H. Recent trends in mucopolysaccharidosis research. J Hum Genet. 2019 Feb;64(2):127-137. doi: 10.1038/s10038-018-0534-8. Epub 2018 Nov 19.
- Background: PubMed 19834056Wilson S, Hashamiyan S, Clarke L, Saftig P, Mort J, Dejica VM, Bromme D. Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities. Am J Pathol. 2009 Nov;175(5):2053-62. doi: 10.2353/ajpath.2009.090211. Epub 2009 Oct 15.
- Background: PubMed 25178906Lalmanach G, Saidi A, Marchand-Adam S, Lecaille F, Kasabova M. Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases. Biol Chem. 2015 Feb;396(2):111-30. doi: 10.1515/hsz-2014-0210.
- Background: PubMed 19388876Bromme D, Lecaille F. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opin Investig Drugs. 2009 May;18(5):585-600. doi: 10.1517/13543780902832661.
- Background: PubMed 28104572Baldo G, Tavares AM, Gonzalez E, Poletto E, Mayer FQ, Matte UD, Giugliani R. Progressive heart disease in mucopolysaccharidosis type I mice may be mediated by increased cathepsin B activity. Cardiovasc Pathol. 2017 Mar-Apr;27:45-50. doi: 10.1016/j.carpath.2017.01.001. Epub 2017 Jan 6.
- Background: PubMed 23968158Sage J, Mallevre F, Barbarin-Costes F, Samsonov SA, Gehrcke JP, Pisabarro MT, Perrier E, Schnebert S, Roget A, Livache T, Nizard C, Lalmanach G, Lecaille F. Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity. Biochemistry. 2013 Sep 17;52(37):6487-98. doi: 10.1021/bi400925g. Epub 2013 Sep 4.
- Background: PubMed 26116954Kubaski F, Tomatsu S, Patel P, Shimada T, Xie L, Yasuda E, Mason R, Mackenzie WG, Theroux M, Bober MB, Oldham HM, Orii T, Shaffer TH. Non-invasive pulmonary function test on Morquio patients. Mol Genet Metab. 2015 Aug;115(4):186-92. doi: 10.1016/j.ymgme.2015.06.007. Epub 2015 Jun 23.
Related trials for Mucopolysaccharidoses
Active, not recruitingObservational study
Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.
Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingPhase 1/2
Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)
Mucopolysaccharidosis Type IIIA
Enrolling by invitationPhase 2/3
An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007
Mucopolysaccharidosis II
Enrolling by invitationPhase 2
Extension Study of Infigratinib in Children With Achondroplasia (ACH)
Achondroplasia
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.
François Labarthe, MD-PhD study director
University Hospital, Tours
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mucopolysaccharidoses, run by University Hospital, Tours at 7 sites in France.
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 12 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 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Evaluation of the expression of pulmonary cathepsins, proteases inhibitors and GAGs in MPS patients. (time frame: Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04112602, which also lists 9 linked publications.
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 4 Jan 2022.