Lysosomal Storage DiseasesNCT03812055
Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders
An observational study of Lysosomal Storage Diseases, run by Lysosomal and Rare Disorders Research and Treatment Center, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will focus on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Lysosomal Storage Diseases
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2018to Jul 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients diagnosed or suspected of having a lysosomal storage disorder and family members of diagnosed patients will be recruited. Informed consent will be obtained prior to the execution of any research procedures.
Who may be able to join
- Subjects with
- confirmed diagnosis of any lysosomal storage disorder
- family members with history of lysosomal storage disorders
Who cannot join
- Subjects excluded from the study include those who:
- present with severe cognitive deficits impairing decision making
- are unable to or for whom it is medically unsafe to withdraw from their current medications, such as subjects on SSRI s and other psychoactive drugs. The subjects on SSRIs may be included in the study only with an approval from the prescribing physician to discontinue their medications temporarily for the study.
- are pregnant or nursing. All women of child bearing potential will undergo a pregnancy test.
- have a history of neurologic conditions such as stroke or any focal brain lesion that may result in parkinonian manifestations. Individuals with such MRI findings will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
LDRTC
Fairfax, Virginia, 22030
Margarita Ivanova, PhD, 703-261-6220, mivanova@ldrtc.org
Ozlem M Goker-Alpan, MD, 7032616220, ogokar-alpan@ldrtc.org
About this study
Official title: Cellular Pharmacodynamics of Small Molecules in Sanfilippo Disease(s) (MPS3) and Other Lysosomal Storage Disorders
The purpose of this study is to evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will focus on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated.
Read the detailed description
Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect on quality of life. The current standard of care of a majority of LSD is enzyme replacement therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease. Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher disease with small molecules acts on ceramide synthesis pathway by decreasing production of the substrate. But, none of the above therapies are effective for treatment of a neuropathic form of LSD. Neurodegenerative changes in the central nervous system are a major problem in Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of neuropathic form of LSD therapy may lie in small molecules acting as agents for enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function. This treatment approach has the potential to cross the CNS and carries the potential to treat the neurological symptoms of Sanfilippo disease or other types of LSD.
The purpose of this study will evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will be focused on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated.
- Conditions
- Lysosomal Storage Diseases
- Medical subject headings
- Lysosomal Storage Diseases
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 |
|---|---|---|
| LSD | Subjects diagnosed or suspected to have any of the following lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease, Mucopolysaccharidoses. | |
| Control | Subjects with no known lysosomal storage disorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect on enzyme activity
To evaluate the effect of small molecules on level of enzyme activity in primary cells derived from patients using fluorometric enzyme assays.
Measured: 24 months
Effect on substrate accumulation
To evaluate the effect of small molecules on heparin sulfate accumulation and substrate accumulation in primary cells derived from patients using techniques like ELISA and mass spectrometry
Measured: 24 months
Effect on autophagy-lysosomal pathway
To evaluate the effect of small molecules on autophagy-lysosomal functions in primary cells derived from patients using commercially available assays
Measured: 24 months
Effect on mitochondrial functions
To evaluate the effect of small molecules on energy metabolism and mitochondrial functions in primary cells derived from patients using commercially available assay kits
Measured: 24 months
Effect on immune and inflammatory response
Examine the immune and inflammatory response to treatment with small molecules using flow cytometry based immunophenotyping
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study start6 Jul 2018
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lysosomal Storage DiseasesStudies 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 only
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lysosomal and Rare Disorders Research and Treatment Center, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margarita M Ivanova, PhD, Principal investigator, LDRTCOzlem Goker-Alpan, MD, Principal investigator, LDRTCRenuka Limgala, PhD, Principal investigator, LDRTC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03812055
- Sponsor's protocol ID
- 18-LDRTC-02
- Status last verified
- Jan 2019
- First submitted
- 18 Jan 2019
- Last updated
- 22 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Pharmacodynamics of Small Molecules in Sanfilippo Disease(s) (MPS3) and Other Lysosomal Storage Disorders
- ClinicalTrials.gov ID
- NCT03812055
- Acronym / sponsor ID
- 18-LDRTC-02
- Conditions
- Lysosomal Storage Diseases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Lysosomal and Rare Disorders Research and Treatment Center, Inc.University, hospital or other
- Study start
- 6 Jul 2018 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 22 Jan 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.
The purpose of this study is to evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will focus on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated.
Detailed description
Lysosomal storage diseases (LSD) often cause severe disability and have a devastating effect on quality of life. The current standard of care of a majority of LSD is enzyme replacement therapy (ERT). ERT, however, becomes less effective during the advanced stages of a disease. Another therapy is substrate reduction therapy (SRT). For example, SRT therapy for Gaucher disease with small molecules acts on ceramide synthesis pathway by decreasing production of the substrate. But, none of the above therapies are effective for treatment of a neuropathic form of LSD. Neurodegenerative changes in the central nervous system are a major problem in Sanfilippo disease. They cause severe disability and behavioral disturbance. This is the main reason for the absence of therapeutic options for MPS3 (Sanfilippo) patients. The future of neuropathic form of LSD therapy may lie in small molecules acting as agents for enzyme-enhancement therapy (EET). EET is based on the ability of small molecules to fold the misfolded mutant enzyme, activate autophagy-lysosomal pathways or mitochondrial function. This treatment approach has the potential to cross the CNS and carries the potential to treat the neurological symptoms of Sanfilippo disease or other types of LSD.
The purpose of this study will evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will be focused on activity of small molecules, in terms of measurements enzymes activity and level of substrates accumulations. Also, the effects of small molecules on cell function, including autophagy-lysosomal pathways, metabolism, mitochondrial function and immune reaction will be investigated.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LSD | – | –Subjects diagnosed or suspected to have any of the following lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease, Mucopolysaccharidoses. |
| Control | – | –Subjects with no known lysosomal storage disorder |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients diagnosed or suspected of having a lysosomal storage disorder and family members of diagnosed patients will be recruited. Informed consent will be obtained prior to the execution of any research procedures.
Key inclusion criteria (3 listed)
- Subjects with
- confirmed diagnosis of any lysosomal storage disorder
- family members with history of lysosomal storage disorders
Key exclusion criteria (5 listed)
- present with severe cognitive deficits impairing decision making
- are unable to or for whom it is medically unsafe to withdraw from their current medications, such as subjects on SSRI s and other psychoactive drugs. The subjects on SSRIs may be included in the study only with an approval from the prescribing physician to discontinue their medications temporarily for the study.
- are pregnant or nursing. All women of child bearing potential will undergo a pregnancy test.
- have a history of neurologic conditions such as stroke or any focal brain lesion that may result in parkinonian manifestations. Individuals with such MRI findings will be excluded from the study.
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
Effect on enzyme activity
Time frame: 24 months
To evaluate the effect of small molecules on level of enzyme activity in primary cells derived from patients using fluorometric enzyme assays.
Effect on substrate accumulation
Time frame: 24 months
To evaluate the effect of small molecules on heparin sulfate accumulation and substrate accumulation in primary cells derived from patients using techniques like ELISA and mass spectrometry
Effect on autophagy-lysosomal pathway
Time frame: 24 months
To evaluate the effect of small molecules on autophagy-lysosomal functions in primary cells derived from patients using commercially available assays
Effect on mitochondrial functions
Time frame: 24 months
To evaluate the effect of small molecules on energy metabolism and mitochondrial functions in primary cells derived from patients using commercially available assay kits
Effect on immune and inflammatory response
Time frame: 24 months
Examine the immune and inflammatory response to treatment with small molecules using flow cytometry based immunophenotyping
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Institute website for more detailsLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Lysosomal Storage Diseases
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Neurological Regression, Myoclonus
RecruitingObservational study
Parkinson's Disease in Type 1 Gaucher Disease
Parkinson Disease (PD), Type 1 Gaucher Disease
RecruitingObservational study
Oxidative Stress and Inflammatory Biomarkers in Gaucher Disease
Gaucher Disease Type I, Oxidative Stress
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.
Margarita M Ivanova, PhD principal investigator
LDRTC
Ozlem Goker-Alpan, MD principal investigator
LDRTC
Renuka Limgala, PhD principal investigator
LDRTC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lysosomal Storage Diseases, run by Lysosomal and Rare Disorders Research and Treatment Center, Inc. at 1 site in United States.
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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Margarita M Ivanova, PhD (7032616220, mivanova@ldrtc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect on enzyme activity (time frame: 24 months). The study lists 5 primary outcomes in all. 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 22 Jan 2019.