Clinical Biomarkers in Alpha-mannosidosis

NCT02141503 | Completed

• 2 other identifiers: 14010614-CH-0106
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Alpha-Mannosidosis

Keywords

Biomarkers; Alpha-Manosidosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline

Secondary Outcomes (1)

• Establish reliable clinical benchmarks for alpha-mannosidosis.

  Ongoing

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Malm D, Nilssen O. Alpha-mannosidosis. Orphanet J Rare Dis. 2008 Jul 23;3:21. doi: 10.1186/1750-1172-3-21.

  PMID: 18651971 BACKGROUND

• Schutzer 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.

  PMID: 20552007 BACKGROUND

• Magnitsky 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.

  PMID: 19743435 BACKGROUND

MeSH Terms

Conditions

alpha-Mannosidosis

Condition Hierarchy (Ancestors)

Mannosidase Deficiency Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Stephen G Kaler, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: July 24, 2014
• Primary Completion: November 29, 2019
• Study Completion: November 29, 2019
• Last Updated: December 3, 2019

Record last verified: 2019-11-29

Locations

US (1)