Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)
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All trials for Hypotonia Cystinuria Syndrome All trials for Isolated PREPL Deficiency All trials of Sulfamethoxazole
-Summary
The investigators will evaluate whether sulfamethoxazole, a sulfamide antibiotic, improves the symptoms of primary PREPL deficiency (hypotonia-cystinuria syndrome and isolated PREPL deficiency).
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+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Treatment | Experimental | Drug: Sulfamethoxazole | Treatment with sulfamethoxazole. Subjects will serve as their own control, by using the data from baseline and after treatment stop. |
- Sulfamethoxazole (Drug): 60 mg sulfamethoxazole per kg bodyweight (maximal of 3g) divided in 2 doses per day during 3 weeks
+Outcome measures
Primary outcomes
- 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
- 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
Secondary outcomes
- 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)
- 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
- 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 muscle strength [Change in strength between baseline/1 week after treatment stop versus third week of treatment]: scored with hand-held manometry
- Change in complete blood count [Change between baseline/1 week after treatment stop versus third week of treatment]: complete blood count (development of cytopenia)
- 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
+Eligibility
Sex: All, ages: 2 Months to any
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
+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. PMID 24610330
+Investigators
- Luc Régal, MD, Principal investigator, Universitair Ziekenhuis Brussel