Alpha-MannosidosisNCT02141503
Clinical Biomarkers in Alpha-mannosidosis
An observational study of Alpha-Mannosidosis, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Background: Alpha-mannosidosis is a rare inherited disorder. It causes problems in many organs and tissues of the body. It can occur in children and adults. Because there is no treatment for this disease, researchers want to find out more about it. Objective: To learn more about Alpha-mannosidosis. Read more about this study
- Who is it for?
- Ages 5 to 60 years
- Conditions the study is for
- Alpha-Mannosidosis
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2014to 29 Nov 2019
- 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 5 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Must have a verifiable diagnosis of AMD based on clinical, biochemical and/or molecular grounds, including increased urinary excretion of mannose-rich oligosaccharides, decreased acidic -mannosidase activity in leukocytes or other nucleated cells, and/or mutations in two alleles of the LAMAN gene.
- Must be at least five years old.
Who cannot join
- Significant systemic or major disease including congestive heart failure, coronary artery disease, cerebrovascular disease and pre-existing or recent onset pulmonary disease, renal failure, organ transplantation, decompensated liver disease, serious psychiatric disease, or malignancy that in the opinion of the investigator would preclude successful participation..
- Pregnancy. We will perform a urine pregnancy test on all post-menarcheal female subjects on the same day as the history and physical exam, prior to MRI. If pregnancy is identified, we will follow Maryland state law in place at the time concerning parental notification. In the event a woman becomes pregnant during the study, she will be withdrawn from all study procedures, but the study team will follow up with the participant regarding the pregnancy outcome.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clinical Biomarkers in Alpha-Mannosidosis
Background:
- Alpha-mannosidosis is a rare inherited disorder. It causes problems in many organs and tissues of the body. It can occur in children and adults. Because there is no treatment for this disease, researchers want to find out more about it.
Read more
Objective:
- To learn more about Alpha-mannosidosis.
Eligibility:
- People ages 5-60 with Alpha-mannosidosis.
Design:
- Participants will be recruited from patient support organizations and medical genetics clinics.
- Participants will have 3 study visits, about once a year. A final evaluation will be made after 3 years.
- Participants will have a medical history and a physical exam.
- Blood samples and a urine sample will be collected.
- Cerebrospinal fluid will be collected. A small area of the lower back will be numbed with medicine. A thin needle will be inserted between the spine bones. About 2 tablespoons of spinal fluid will be removed.
- Brain magnetic resonance spectroscopy (MRS) scans will be done at each visit. MRS uses a strong magnetic field and radio waves to take pictures of chemicals in the brain with a scanner. The participant will lie on a table that can slide in and out of the cylinder. While in the scanner the participant will hear loud knocking noises. They will get earplugs or earmuffs to muffle the sound. Medicines might be used to keep the participant asleep during the MRS.
- Participants will have a skin biopsy at the first visit only. A small area of the participant s skin will be numbed. A small circle of skin will be removed with a biopsy tool.
Read the detailed description
Alpha-mannosidosis (AMD) is an inherited lysosomal storage disorder caused by mutations in the LAMAN gene, which encodes lysosomal alpha-mannosidase and is characterized by neurodevelopmental delay, mild immune deficiency, facial and skeletal abnormalities, hearing impairment, intellectual disability, muscle weakness and ataxia. The progression of neuromuscular and skeletal deterioration is insidious, occurring over several decades, rendering most patients wheel-chair dependent. No consistently successful treatment is available. To better characterize the biochemical phenotype and natural history of this disorder, we will study 15 patients with AMD, ranging in age from five to 60 years, recruited from Departments of Biochemical Genetics and Medical Genetics at university medical centers mainly in the US and Canada or referred by the Intl Society for Mannosidosis \& Related Diseases. Participants in the study will visit the NIH Clinical Center 2-3 days on an outpatient basis and will undergo clinical and biochemical evaluations to establish reliable clinical
benchmarks and to identify cerebrospinal fluid biomarkers that could serve as candidate
surrogate markers of treatment effect in future clinical trials. The protocol will take advantage of the NICHD Biomedical Mass Spectrometry Facility to generate CSF proteomic profiles. Patients will also undergo MR spectroscopy (under sedation/anesthesia, if appropriate) in order to establish the phenotypic baseline and for possible utility as a guide for natural history and/or treatment outcomes in future studies. If the pre-clinical components of this proposal prove promising, the prospect of a recombinant adeno-associated viral gene therapy trial involving a brain-directed (intrathecal) approach for AMD would be possible within 3 years.
- Conditions
- Alpha-Mannosidosis
- Keywords
- Biomarkers, Alpha-Manosidosis
- Medical subject headings
- alpha-Mannosidosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial.
Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial.
Measured: Baseline
Secondary outcomes (1)
Establish reliable clinical benchmarks for alpha-mannosidosis.
Establish reliable clinical benchmarks for alpha-mannosidosis.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2014 (estimated)
- Study start24 Jul 2014
- Primary completion29 Nov 2019
- Study completion29 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alpha-MannosidosisStudies 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
- Cohort
- Time perspective
- Other
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephen G Kaler, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141503
- Sponsor's protocol ID
- 140106
- Other IDs
- 14-CH-0106
- Status last verified
- 29 Nov 2019
- First submitted
- 15 May 2014
- Last updated
- 3 Dec 2019
- Results posted
- No
Publications
Malm D, Nilssen O. Alpha-mannosidosis. Orphanet J Rare Dis. 2008 Jul 23;3:21. doi: 10.1186/1750-1172-3-21.
PubMed 18651971Schutzer SE, Liu T, Natelson BH, Angel TE, Schepmoes AA, Purvine SO, Hixson KK, Lipton MS, Camp DG, Coyle PK, Smith RD, Bergquist J. Establishing the proteome of normal human cerebrospinal fluid. PLoS One. 2010 Jun 11;5(6):e10980. doi: 10.1371/journal.pone.0010980.
PubMed 20552007Magnitsky S, Vite CH, Delikatny EJ, Pickup S, Wehrli S, Wolfe JH, Poptani H. Magnetic resonance spectroscopy of the occipital cortex and the cerebellar vermis distinguishes individual cats affected with alpha-mannosidosis from normal cats. NMR Biomed. 2010 Jan;23(1):74-9. doi: 10.1002/nbm.1430.
PubMed 19743435
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Biomarkers in Alpha-Mannosidosis
- ClinicalTrials.gov ID
- NCT02141503
- Acronym / sponsor ID
- 140106
- Conditions
- Alpha-Mannosidosis
- Keywords
- Biomarkers, Alpha-Manosidosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 24 Jul 2014
- Primary completion
- 29 Nov 2019 (actual)
- Study completion
- 29 Nov 2019 (actual)
- First posted
- 19 May 2014 (estimated)
- 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.
Background:
- Alpha-mannosidosis is a rare inherited disorder. It causes problems in many organs and tissues of the body. It can occur in children and adults. Because there is no treatment for this disease, researchers want to find out more about it.
Objective:
- To learn more about Alpha-mannosidosis.
Eligibility:
- People ages 5-60 with Alpha-mannosidosis.
Design:
- Participants will be recruited from patient support organizations and medical genetics clinics.
- Participants will have 3 study visits, about once a year. A final evaluation will be made after 3 years.
- Participants will have a medical history and a physical exam.
- Blood samples and a urine sample will be collected.
- Cerebrospinal fluid will be collected. A small area of the lower back will be numbed with medicine. A thin needle will be inserted between the spine bones. About 2 tablespoons of spinal fluid will be removed.
- Brain magnetic resonance spectroscopy (MRS) scans will be done at each visit. MRS uses a strong magnetic field and radio waves to take pictures of chemicals in the brain with a scanner. The participant will lie on a table that can slide in and out of the cylinder. While in the scanner the participant will hear loud knocking noises. They will get earplugs or earmuffs to muffle the sound. Medicines might be used to keep the participant asleep during the MRS.
- Participants will have a skin biopsy at the first visit only. A small area of the participant s skin will be numbed. A small circle of skin will be removed with a biopsy tool.
Detailed description
Alpha-mannosidosis (AMD) is an inherited lysosomal storage disorder caused by mutations in the LAMAN gene, which encodes lysosomal alpha-mannosidase and is characterized by neurodevelopmental delay, mild immune deficiency, facial and skeletal abnormalities, hearing impairment, intellectual disability, muscle weakness and ataxia. The progression of neuromuscular and skeletal deterioration is insidious, occurring over several decades, rendering most patients wheel-chair dependent. No consistently successful treatment is available. To better characterize the biochemical phenotype and natural history of this disorder, we will study 15 patients with AMD, ranging in age from five to 60 years, recruited from Departments of Biochemical Genetics and Medical Genetics at university medical centers mainly in the US and Canada or referred by the Intl Society for Mannosidosis \& Related Diseases. Participants in the study will visit the NIH Clinical Center 2-3 days on an outpatient basis and will undergo clinical and biochemical evaluations to establish reliable clinical
benchmarks and to identify cerebrospinal fluid biomarkers that could serve as candidate
surrogate markers of treatment effect in future clinical trials. The protocol will take advantage of the NICHD Biomedical Mass Spectrometry Facility to generate CSF proteomic profiles. Patients will also undergo MR spectroscopy (under sedation/anesthesia, if appropriate) in order to establish the phenotypic baseline and for possible utility as a guide for natural history and/or treatment outcomes in future studies. If the pre-clinical components of this proposal prove promising, the prospect of a recombinant adeno-associated viral gene therapy trial involving a brain-directed (intrathecal) approach for AMD would be possible within 3 years.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 5 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
Key exclusion criteria (2 listed)
- Significant systemic or major disease including congestive heart failure, coronary artery disease, cerebrovascular disease and pre-existing or recent onset pulmonary disease, renal failure, organ transplantation, decompensated liver disease, serious psychiatric disease, or malignancy that in the opinion of the investigator would preclude successful participation..
- Pregnancy. We will perform a urine pregnancy test on all post-menarcheal female subjects on the same day as the history and physical exam, prior to MRI. If pregnancy is identified, we will follow Maryland state law in place at the time concerning parental notification. In the event a woman becomes pregnant during the study, she will be withdrawn from all study procedures, but the study team will follow up with the participant regarding the pregnancy outcome.
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
Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial.
Time frame: Baseline
Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial.
1 secondary outcome
Establish reliable clinical benchmarks for alpha-mannosidosis.
Time frame: Ongoing
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 3 Dec 2019.
- Background: PubMed 18651971Malm D, Nilssen O. Alpha-mannosidosis. Orphanet J Rare Dis. 2008 Jul 23;3:21. doi: 10.1186/1750-1172-3-21.
- Background: PubMed 20552007Schutzer SE, Liu T, Natelson BH, Angel TE, Schepmoes AA, Purvine SO, Hixson KK, Lipton MS, Camp DG, Coyle PK, Smith RD, Bergquist J. Establishing the proteome of normal human cerebrospinal fluid. PLoS One. 2010 Jun 11;5(6):e10980. doi: 10.1371/journal.pone.0010980.
- Background: PubMed 19743435Magnitsky S, Vite CH, Delikatny EJ, Pickup S, Wehrli S, Wolfe JH, Poptani H. Magnetic resonance spectroscopy of the occipital cortex and the cerebellar vermis distinguishes individual cats affected with alpha-mannosidosis from normal cats. NMR Biomed. 2010 Jan;23(1):74-9. doi: 10.1002/nbm.1430.
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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.
Stephen G Kaler, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 Alpha-Mannosidosis, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 2 inclusion and 2 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 3 Dec 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?
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?
Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial. (time frame: Baseline). 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 NCT02141503, which also lists 3 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 3 Dec 2019.