Sulfamethoxazole for the Treatment of Primary PREPL Deficiency

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

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

Conditions
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Hypotonia Cystinuria Syndrome, Isolated PREPL Deficiency

Intervention / Treatment
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* Drug: Sulfamethoxazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |