PREPL in Health and Disease (PHD)

Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient patients

Study Overview

• Status: Unknown
• Conditions: Obesity; Healthy Volunteers; Prader-Willi Syndrome; Muscle Hypotonia; Hypotonia-Cystinuria Syndrome; Dwarfism, Growth Hormone Deficiency
• Intervention / Treatment: Procedure: Blood draw; Procedure: muscle biopsy

Detailed Description

PREPL is defective in hypotonia cystinuria syndrome and in isolated PREPL deficiency. The investigators have constructed a blood test to evaluate PREPL activity in patients with possible PREPL deficiency.

The study will determine normal values for age (0-18) for PREPL activity in blood.

Also, patients with a clinical phenotype that overlaps with PREPL deficiency (including patients with known primary PREPL deficiency and Prader-Willi syndrome) will be evaluated for PREPL activity in blood.

A last part of the study will involve muscle biopsies during elective anesthesia/surgery for other reasons. There will be 2 groups: patients without signs of PREPL deficiency undergoing surgery (controls) and patients with Prader-Willi syndrome undergoing anesthesia or surgery (patients). The control group will be age-matched to the hypotonia group. In the muscle biopsies, PREPL activity and expression will be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 125
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luc Régal, MD; Phone Number: 003216343820; Email: Luc.regal@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZLeuven
    • Contact: Luc Régal, MD; Phone Number: 003216343820; Email: Luc.regal@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• According to group
• Control group: children seen at a postinfectious consultation

Exclusion Criteria:

• Control group: symptoms overlapping with PREPL deficiency, genetic or syndromic disease, atypically developing children
• other groups: contraindication for blood draw
• group with muscle biopsy: contra-indication for muscle biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control Blood; Patients on routine postinfectious control, blood draw	Procedure: Blood draw; Blood draw
Experimental: Primary PREPL deficiency Blood; Patients with primary PREPL deficiency, blood draw	Procedure: Blood draw; Blood draw
Experimental: Prader Willi syndrome Blood; Patients with Prader-Willi syndrome, blood draw	Procedure: Blood draw; Blood draw
Experimental: Primary PREPL deficiency like Blood; Patients with symptoms overlapping with primary PREPL deficiency (like hypotonia, growth hormone deficiency, obesity), blood draw	Procedure: Blood draw; Blood draw
Experimental: Control muscle; Patients without hypotonia, growth hormone deficiency, obesity, undergoing elective surgery, muscle biopsy from the surgical site and blood draw	Procedure: Blood draw; Blood draw; Procedure: muscle biopsy; Muscle biopsy during planned anesthesia/surgery
Experimental: Prader-Willli syndrome muscle; Patients with Prader-Willi syndrome undergoing elective anesthesia or surgery, muscle biopsy (from surgical site if applicable) and blood draw	Procedure: Blood draw; Blood draw; Procedure: muscle biopsy; Muscle biopsy during planned anesthesia/surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PREPL activity (ng active PREPL/g protein) normal values in blood	normal values for PREPL activity	3 months
PREPL activity in patients with Prader Willi syndrome compared to activity in normal controls	Comparison of PREPL activity in blood and muscle between above mentioned groups	3 months
PREPL activity in patients with primary PREPL deficiency compared to activity in normal controls	Comparison of PREPL activity in blood between above mentioned groups	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls	exploratory evaluation	3 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Luc Régal, MD, KU Leuven

Publications and helpful links

General Publications

• Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014 Apr 8;82(14):1254-60. doi: 10.1212/WNL.0000000000000295. Epub 2014 Mar 7.
• Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. doi: 10.1086/498852. Epub 2005 Nov 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): January 1, 2015
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimate): October 13, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Neuromuscular Manifestations; Hypothalamic Diseases; Bone Diseases; Intellectual Disability; Renal Tubular Transport, Inborn Errors; Bone Diseases, Endocrine; Pituitary Diseases; Abnormalities, Multiple; Chromosome Disorders; Obesity; Bone Diseases, Developmental; Hypopituitarism; Renal Aminoacidurias; Syndrome; Prader-Willi Syndrome; Dwarfism, Pituitary; Cystinuria; Dwarfism; Muscle Hypotonia
• Other Study ID Numbers: S57206