Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (SPPD)

Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)

The investigators will evaluate whether sulfamethoxazole, a sulfamide antibiotic, improves the symptoms of primary PREPL deficiency (hypotonia-cystinuria syndrome and isolated PREPL deficiency).

Study Overview

• Status: Unknown
• Conditions: Hypotonia Cystinuria Syndrome; Isolated PREPL Deficiency
• Intervention / Treatment: Drug: Sulfamethoxazole

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with molecular confirmation of primary PREPL deficiency
• who are able to follow the study protocol (for the primary endpoint)
• who have given written informed consent

Exclusion Criteria:

• age<2m
• women of child-bearing age unless using a reliable method for contraception and not pregnant at study entrance
• additional diagnosis with influence on muscle force
• not able to follow the study protocol (for the primary endpoint)
• history of sulfonamide hypersensitivity
• diminished renal function based on serum creatinine
• transaminases higher than 3 times the upper limit of normal
• for the pupillometry: eye pathology with the exception of refractive errors, drugs with influence on the pupillary light reflex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Treatment with sulfamethoxazole. Subjects will serve as their own control, by using the data from baseline and after treatment stop.	Drug: Sulfamethoxazole; 60 mg sulfamethoxazole per kg bodyweight (maximal of 3g) divided in 2 doses per day during 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ptosis on myasthenia gravis composite scale	ptosis item on the myasthenia gravis composite scale: single blinded scoring on video-images	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in ptosis index	ptosis index, single blinded measurement on photograph	Change in index between baseline/1 week after treatment stop versus third week of treatment
Change in lip length index	lip length index, single blinded measurement on photographs	Change in index between baseline/1 week after treatment stop versus third week of treatment
Change in lip purse index	Lip purse index, single blinded measurement on photographs	Change in index between baseline/1 week after treatment stop versus third week of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in satiety	satiety scale (visual analog); 4 questions are asked, a compositie score is made, by adding the different scores (the answers on questions 2 and 3 are counted as negative values)	Change in Composite score between baseline/1 week after treatment stop versus third week of treatment
Change in myasthenia gravis composite score	Sum of all the subscores	Change in score between baseline/1 week after treatment stop versus third week of treatment
myasthenia gravis composite dysarthria and eye closure subscores	scored on video	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in muscle strength	scored with hand-held manometry	Change in strength between baseline/1 week after treatment stop versus third week of treatment
Change in complete blood count	complete blood count (development of cytopenia)	Change between baseline/1 week after treatment stop versus third week of treatment
Change in Glycemia	Glycemia	Change between baseline/1 week after treatment stop versus third week of treatment
Change in renal ultrasound	renal ultrasound	development of kidney stones after the third week of treatment versus baseline
Change in myasthenia gravis-activities of daily life	Scale with rating of activities of daily life	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in neuropsychology Child Behaviour checklist	composite score of Child Behaviour checklist	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in neuropsychology Brief	composite score of Brief	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in neuropsychology Amsterdamse neuropsychologische test	composite score of Amsterdamse Neuropsychologische test (ANT)	Change in score between baseline/1 week after treatment stop versus third week of treatment
Change in Insulin	insulin	Change between baseline/1 week after treatment stop versus third week of treatment
Change in IGF1	IGF-1	Change between baseline/1 week after treatment stop versus third week of treatment
Change in IGFPB3	IGFBP3	Change between baseline/1 week after treatment stop versus third week of treatment
Change in pupillometry	dynamic pupillometry with infrared camera	Change between baseline/1 week after treatment stop versus third week of treatment

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Luc Régal, MD, Universitair Ziekenhuis Brussel

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.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: December 22, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Estimate): December 29, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Kidney Diseases; Urologic Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neuromuscular Manifestations; Renal Tubular Transport, Inborn Errors; Renal Aminoacidurias; Cystinuria; Muscle Hypotonia; Anti-Infective Agents; Sulfamethoxazole
• Other Study ID Numbers: 2015/059