Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00078078
Status:
RECRUITING
Last Update Posted:
2024-06-26
First Post:
2004-02-18
Brief Title:
Clinical and Laboratory Study of Methylmalonic Acidemia
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Clinical and Basic Investigations of Methylmalonic Acidemia MMA and Related Disorders
Status:
RECRUITING
Status Verified Date:
2024-09-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Methylmalonic acidemia MMA one of the most common inborn errors of organic acid metabolism is heterogeneous in etiology and clinical manifestations Affected patients with cblA cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia pancreatitis end stage renal failure growth impairment osteoporosis and developmental delay The frequency of these complications and their precipitants remain undefined Furthermore current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population Increasingly solid organ transplantation liver andor kidney has been used to treat patients Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as hyperhomocysteinemia These conditions are named after the corresponding cellular complementation class cblC cblD cblF cblJ and cblX and are also heterogenous clinically and biochemically The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature hyperhomocysteinemia Lastly a group of patients can have increased methylmalonic acid andor homocysteine in the blood or urine caused by variantsin recently identified ACSF3 and unknown genes
In this protocol we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects Routine inpatient admissions will last up to 4-5 days and involve urine collection blood drawing ophthalmological examination radiological procedures MRIMRS skin biopsies in some and developmental testing In a subset of patients who have or will receive renal hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA a lumbar puncture to examine CSF metabolites will be performed In this small group of patients CSF metabolite monitoring may be used to adjust therapy
The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies query for genotypeenzymaticphenotype correlations search for new genetic causes of methylmalonic acidemia andor homocysteinemia identify new disease biomarkers and define clinical outcome parameters for future clinical trials
The population will consist of participants previously evaluated at NIH physician referrals and families directed to the study from clinicaltrialsgov as well as the Organic Acidemia Association Homocystinuria Network America and other national and international support groups Most participants will be evaluated only at the NIH Clinical Center However if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol that patient may enroll at the Children s National Medical Center CNMC site pending approval by Dr Chapman the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely Outcome measures will largely be descriptive and encompass correlations between clinical biochemical and molecular parameters
In this protocol we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects Routine inpatient admissions will last up to 4-5 days and involve urine collection blood drawing ophthalmological examination radiological procedures MRIMRS skin biopsies in some and developmental testing In a subset of patients who have or will receive renal hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA a lumbar puncture to examine CSF metabolites will be performed In this small group of patients CSF metabolite monitoring may be used to adjust therapy
The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies query for genotypeenzymaticphenotype correlations search for new genetic causes of methylmalonic acidemia andor homocysteinemia identify new disease biomarkers and define clinical outcome parameters for future clinical trials
The population will consist of participants previously evaluated at NIH physician referrals and families directed to the study from clinicaltrialsgov as well as the Organic Acidemia Association Homocystinuria Network America and other national and international support groups Most participants will be evaluated only at the NIH Clinical Center However if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol that patient may enroll at the Children s National Medical Center CNMC site pending approval by Dr Chapman the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely Outcome measures will largely be descriptive and encompass correlations between clinical biochemical and molecular parameters
Detailed Description:
Methylmalonic acidemia MMA one of the most common inborn errors of organic acid metabolism is heterogeneous in etiology and clinical manifestations Affected patients with mut cblA and cblB classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia pancreatitis end stage renal failure growth impairment osteoporosis and developmental delay The frequency of these complications and their precipitants remain undefined Furthermore current outcomes have continued to demonstrate substantial morbidity and mortality in the patient population Increasingly solid organ transplantation liver andor kidney has been used to treat patients Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as hyperhomocysteinemia These conditions are named after the corresponding cellular complementation class cblC cblD cblF cblJ and cblX and are also heterogeneous clinically and biochemically The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature hyperhomocysteinemia Lastly a group of patients can have increased methylmalonic acid andor homocysteine andor malonic acid in the blood or urine caused by variants in recently identified ACSF3 and unknown genes
In this protocol we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects Routine inpatient admissions and outpatient evaluations will last up to 4-5 days and involve urine collection blood drawing ophthalmological examination radiological procedures MRIMRS skin biopsies in some and developmental testing
The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies query for genotypeenzymaticphenotype correlations search for new genetic causes of methylmalonic acidemia andor homocysteinemia identify new disease biomarkers and define clinical outcome parameters for future clinical trials The population will consist of participants previously evaluated at NIH physician referrals and families directed to the study from clinicaltrialsgov as well as the Organic Acidemia Association Homocystinuria Network America and other national and international support groups Most participants will be evaluated only at the NIH Clinical Center However if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol that patient may enroll at the Children s National Medical Center CNMC site pending approval by Dr Chapman the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely Outcome measures will largely be descriptive and encompass correlations between clinical biochemical and molecular parameters
In this protocol we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects Routine inpatient admissions and outpatient evaluations will last up to 4-5 days and involve urine collection blood drawing ophthalmological examination radiological procedures MRIMRS skin biopsies in some and developmental testing
The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies query for genotypeenzymaticphenotype correlations search for new genetic causes of methylmalonic acidemia andor homocysteinemia identify new disease biomarkers and define clinical outcome parameters for future clinical trials The population will consist of participants previously evaluated at NIH physician referrals and families directed to the study from clinicaltrialsgov as well as the Organic Acidemia Association Homocystinuria Network America and other national and international support groups Most participants will be evaluated only at the NIH Clinical Center However if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol that patient may enroll at the Children s National Medical Center CNMC site pending approval by Dr Chapman the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely Outcome measures will largely be descriptive and encompass correlations between clinical biochemical and molecular parameters
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-HG-0127 | None | None | None |