Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia
People s bodies need to break down food into the chemicals. These chemicals are used for energy and growth. Some people cannot process all chemicals very well. Too much of some chemicals can cause diseases. One of these diseases is called propionic acidemia (PA). People with PA can have problems with growth, learning heart, abdomen, and other organs. Researchers want to better understand how these problems happen.
To learn more about propionic acidemia and the genes that might contribute to it.
People at least 2 years old with PA who can travel to the clinic
Some unaffected family members
Participants will have a 3 to 5-day hospital visit every year or every few years. Family members may have just 1 visit.
During the family member visit, they may have:
Samples of blood and urine
Questions about diet and a food diary
Doctors and nurses may do additional studies:
Samples of saliva, skin and stool
Fluid from a gastronomy tube, if participants have one
Dental and eye evaluations
A kidney test - a small amount of dye will be injected and blood will be collected.
Consultations with specialists
A test of calories needed at rest. A clear plastic tent is placed over the participant to measure breathing.
Stable isotope study. Participants will take a nonradioactive substance then blow into a bag.
Photos taken of the face and body with underwear on
Ultrasound of the abdomen
Participants may have other tests if study doctors recommend them. They will get the results of standard medical tests and genetic tests.
|Study Design:||Time Perspective: Prospective|
|Official Title:||The Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia|
- The study is non-interventional, prospective [ Time Frame: Study Completion ]
|Study Start Date:||July 28, 2016|
|Estimated Study Completion Date:||August 1, 2030|
|Estimated Primary Completion Date:||August 1, 2030 (Final data collection date for primary outcome measure)|
Propionic acidemia (PA) is one of the most common inborn errors of organic acid metabolism. Although this disorder is now routinely detected in the immediate neonatal period on the US newborn screen, clinical outcomes are poor despite timely and aggressive medical intervention [Kolker, Cazorla, et al 2015; Leonard et al 2003]. Worldwide, the incidence of PA varies widely. The estimated live-birth incidence of PA is 1:105,000-130,000 in the US [Chace et al 2001; Couce et al 2011], 1:166,000 in Italy [Dionisi-Vici et al 2002] and 1:250,000 in Germany [Schulze et al 2003]. Affected patients are medically fragile and can suffer from complications such as failure to thrive, intellectual disability, basal ganglia strokes, seizures, cardiomyopathy, cardiac arrhythmias, pancreatitis, impaired gut motility, and hematological complications. The frequency of these complications in the US patients and their precipitants remain undefined. Furthermore, current treatment outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Specific treatments include dietary modification to reduce propiogenic precursor load, levocarnitine to facilitate excretion of propionate, and oral antibiotics to suppress propiogenic gut flora. More recently, solid organ transplantation (liver and/or kidney) has been used to treat PA patients. However, optimal transplant strategy and posttransplant
management are incompletely understood.
Several survey-based and retrospective studies describing the natural history of propionic acidemia have been published in the last decade [Baumgartner et al 2014; Kolker, Cazorla, et al 2015; Kolker, Valayannopoulos, et al 2015; Kraus et al 2012; Nizon et al 2013; Pena & Burton 2012; Pena, Franks, et al 2012]. While these publications added to our understanding of the clinical course of this disease, the studies have not systematically focused on the US population using prospective analysis and reflect largely European experience, where many developed countries do not routinely screen for PA using newborn screen. Thus, the benefits of newborn
screening on the PA outcomes require further clarification [Grunert et al 2012].
Under proposed NIH protocol, we will prospectively evaluate patients with propionic acidemia with special emphasis on the US population. Routine inpatient admissions and outpatient evaluations will last 4-5 days and involve blood drawing, urine collection, stool collections, genomic studies, ophthalmological examination, cardiology evaluation, radiological procedures, brain and cardiac MRI/MRS, dietary assessment and neurobehavioral evaluation. In some patients skin biopsies will be pursued.
The study objectives will be to describe the natural history of propionic acidemia in the US patients by delineating the spectrum of phenotypes and querying for genotype, enzymology, microbiome, and phenotype correlations. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov, Organic Acidemia Association and Propionic Acidemia Foundation. Patients will be evaluated at the NIH Clinical Center. Outcome measures will largely be descriptive and encompass correlations between clinical, microbiological, biochemical and molecular parameters.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02890342
|Contact: Charles P Venditti, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Charles P Venditti, M.D.||National Human Genome Research Institute (NHGRI)|