Sulfamethoxazole for the Treatment of Primary PREPL Deficiency

Phase 2

• Conditions: Hypotonia Cystinuria Syndrome; Isolated PREPL Deficiency
• Interventions: Drug: Sulfamethoxazole

• Registration Number: NCT02640443
• Lead Sponsor: Universitair Ziekenhuis Brussel

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2015-10
• Study Start: 2015-10
• Study First Submitted: 2015-10-07
• Study First Submitted QC: 2015-12-22
• Last Update Submitted: 2015-12-22
• Study First Posted: 2015-12-29
• Last Update Posted: 2015-12-29
• Primary Completion: 2016-10
• Study Completion: 2016-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Sulfamethoxazole	Treatment with sulfamethoxazole. Subjects will serve as their own control, by using the data from baseline and after treatment stop.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in muscle strength	Change in strength between baseline/1 week after treatment stop versus third week of treatment	scored with hand-held manometry
Change in myasthenia gravis composite score	Change in score between baseline/1 week after treatment stop versus third week of treatment	Sum of all the subscores
Change in satiety	Change in Composite score between baseline/1 week after treatment stop versus third week of treatment	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)
myasthenia gravis composite dysarthria and eye closure subscores	Change in score between baseline/1 week after treatment stop versus third week of treatment	scored on video
Change in Glycemia	Change between baseline/1 week after treatment stop versus third week of treatment	Glycemia
Change in renal ultrasound	development of kidney stones after the third week of treatment versus baseline	renal ultrasound
Change in myasthenia gravis-activities of daily life	Change in score between baseline/1 week after treatment stop versus third week of treatment	Scale with rating of activities of daily life
Change in neuropsychology Child Behaviour checklist	Change in score between baseline/1 week after treatment stop versus third week of treatment	composite score of Child Behaviour checklist
Change in neuropsychology Brief	Change in score between baseline/1 week after treatment stop versus third week of treatment	composite score of Brief
Change in neuropsychology Amsterdamse neuropsychologische test	Change in score between baseline/1 week after treatment stop versus third week of treatment	composite score of Amsterdamse Neuropsychologische test (ANT)
Change in Insulin	Change between baseline/1 week after treatment stop versus third week of treatment	insulin
Change in IGF1	Change between baseline/1 week after treatment stop versus third week of treatment	IGF-1
Change in IGFPB3	Change between baseline/1 week after treatment stop versus third week of treatment	IGFBP3
Change in pupillometry	Change between baseline/1 week after treatment stop versus third week of treatment	dynamic pupillometry with infrared camera
Change in complete blood count	Change between baseline/1 week after treatment stop versus third week of treatment	complete blood count (development of cytopenia)