MR Spectroscopy and Disease Severity Score for Gaucher in Pediatric Population (MRS in Gaucher)

Quantification of Bone Marrow Involvement in Gaucher Disease With Proton MR Spectroscopy, Correlation With Bone Marrow Burden Score, Genotype and Disease Severity Score for Pediatric Patients

The bone status in Gaucher disease is very difficult to monitor precisely in children. This is a major problem because lack of optimal treatment, especially enzyme replacement, may cause irreversible severe bone damage that will impact an affected person's life. Currently, there are qualitative (subjective) methods, such as Magnetic resonance Imaging (MRI), to gauge the response to treatment. A quantitative (objective) measurement of Gaucher cell presence and activity in bone marrow could help with more precise and accurate monitoring of bone marrow disease in patients both treated and not (yet) being treated with enzyme replacement. The investigators will evaluate the efficacy of Magnetic Resonance Spectroscopy (MRS) as a quantitative assessment of bone marrow involvement in Children with Gaucher, and examine how this result correlates with semiquantitative MRI scales and overall disease severity.

Study Overview

• Status: Completed
• Conditions: Gaucher

Detailed Description

To quantify the amount of fat in the bone marrow of affected subjects and healthy controls the investigators will use Single voxel short, echo time(TE) proton spectroscopy. This MR Spectroscopy (MRS) will be conducted in the vertebral body of L5 and in the neck of the femur.

To assess the qualitative scores and compare it to the quantitative MR Spectroscopy (MRS) results the investigators will use a series of Fluid sensitive and Fat sensitive conventional MR sequences that will allows us to determine indirectly the degree of glucocerebrosidase infiltration.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will enroll patients with a Diagnosis of Gaucher disease. Subjects will be between 5 and 20 years of age. We will recruit an equal number of age and gender matched healthy volunteers.

Description

Inclusion Criteria:

• Confirmed diagnosis of Gaucher disease / age and gender match control
• Children aged 5-20 yrs
• Parental consent
• Child assent if appropriate

Exclusion Criteria:

• Presence of medical illness or exposure to drugs that alter the appearance of bone marrow on MRI
• Contraindication for MRI
• Likelihood for claustrophobia
• Non cooperative patient
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Gaucher; We will enroll 15 children who have a confirmed diagnosis of Gaucher disease.
Healthy volunteers; We will enroll 15 age and gender matched controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the fat fraction (quantified by MRS) between subjects with Gaucher disease and controls.	We will measure the fat fraction only once, at the time of recruitment. We will compare the fat fraction of an affected subject to that of an age matched control. We will determine if significant difference exist.	within 5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the semiquantitative MRI scores between affected subjects and controls	We will compare the ordinal data obtained from applying two semiquantitative severity scores: Bone marrow burden (BMB) and Spanish MRI (S-MRI).	within 5 minutes

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Diego Jaramillo, MD, MPH, Children's Hospital of Philadelphia; Study Chair: Paige Kaplan, MBBCh, Children's Hospital of Philadelphia; Study Director: Maria A Bedoya, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H, Martins AM, Sawyer C, vom Dahl S, Yeh MS, Zimran A. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med. 2010 Jan;12(1):44-51. doi: 10.1097/GIM.0b013e3181c39194.
• Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med. 2006 Jun;160(6):603-8. doi: 10.1001/archpedi.160.6.603.
• Maas M, van Kuijk C, Stoker J, Hollak CE, Akkerman EM, Aerts JF, den Heeten GJ. Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging--initial experience. Radiology. 2003 Nov;229(2):554-61. doi: 10.1148/radiol.2292020296. Epub 2003 Oct 2.
• Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000 Oct 9;160(18):2835-43. doi: 10.1001/archinte.160.18.2835.
• Roca M, Mota J, Alfonso P, Pocovi M, Giraldo P. S-MRI score: A simple method for assessing bone marrow involvement in Gaucher disease. Eur J Radiol. 2007 Apr;62(1):132-7. doi: 10.1016/j.ejrad.2006.11.024. Epub 2006 Dec 11.
• Maas M, Hangartner T, Mariani G, McHugh K, Moore S, Grabowski GA, Kaplan P, Vellodi A, Yee J, Steinbach L. Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease. Skeletal Radiol. 2008 Mar;37(3):185-8. doi: 10.1007/s00256-007-0425-0. No abstract available.
• Baldellou A, Andria G, Campbell PE, Charrow J, Cohen IJ, Grabowski GA, Harris CM, Kaplan P, McHugh K, Mengel E, Vellodi A. Paediatric non-neuronopathic Gaucher disease: recommendations for treatment and monitoring. Eur J Pediatr. 2004 Feb;163(2):67-75. doi: 10.1007/s00431-003-1363-z. Epub 2003 Dec 16.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimate): July 19, 2011

Study Record Updates

• Last Update Posted (Estimate): February 4, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: MRI; Magnetic resonance Spectroscopy; Lysosomal diseases
• Other Study ID Numbers: 11-008013