Clinical trial NCT02640443: Sulfamethoxazole for the Treatment of Primary PREPL Deficiency
Official title: Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hypotonia Cystinuria Syndrome
Isolated PREPL Deficiency
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2015-12-29
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Change in ptosis on myasthenia gravis composite scale
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in ptosis index
timeFrame: Change in index between baseline/1 week after treatment stop versus third week of treatment
measure: Change in lip length index
timeFrame: Change in index between baseline/1 week after treatment stop versus third week of treatment
measure: Change in lip purse index
timeFrame: Change in index between baseline/1 week after treatment stop versus third week of treatment
Secondary outcomes:
measure: Change in satiety
timeFrame: Change in Composite score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in myasthenia gravis composite score
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: myasthenia gravis composite dysarthria and eye closure subscores
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in muscle strength
timeFrame: Change in strength between baseline/1 week after treatment stop versus third week of treatment
measure: Change in complete blood count
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
measure: Change in Glycemia
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
measure: Change in renal ultrasound
timeFrame: development of kidney stones after the third week of treatment versus baseline
measure: Change in myasthenia gravis-activities of daily life
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in neuropsychology Child Behaviour checklist
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in neuropsychology Brief
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in neuropsychology Amsterdamse neuropsychologische test
timeFrame: Change in score between baseline/1 week after treatment stop versus third week of treatment
measure: Change in Insulin
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
measure: Change in IGF1
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
measure: Change in IGFPB3
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
measure: Change in pupillometry
timeFrame: Change between baseline/1 week after treatment stop versus third week of treatment
Other outcomes:
Locations:
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Luc Régal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.