Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (SPPD)
Primary Purpose
Hypotonia Cystinuria Syndrome, Isolated PREPL Deficiency
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sulfamethoxazole
Sponsored by
About this trial
This is an interventional treatment trial for Hypotonia Cystinuria Syndrome
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
Treatment with sulfamethoxazole. Subjects will serve as their own control, by using the data from baseline and after treatment stop.
Outcomes
Primary Outcome Measures
Change in ptosis on myasthenia gravis composite scale
ptosis item on the myasthenia gravis composite scale: single blinded scoring on video-images
Change in ptosis index
ptosis index, single blinded measurement on photograph
Change in lip length index
lip length index, single blinded measurement on photographs
Change in lip purse index
Lip purse index, single blinded measurement on photographs
Secondary Outcome Measures
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 myasthenia gravis composite score
Sum of all the subscores
myasthenia gravis composite dysarthria and eye closure subscores
scored on video
Change in muscle strength
scored with hand-held manometry
Change in complete blood count
complete blood count (development of cytopenia)
Change in Glycemia
Glycemia
Change in renal ultrasound
renal ultrasound
Change in myasthenia gravis-activities of daily life
Scale with rating of activities of daily life
Change in neuropsychology Child Behaviour checklist
composite score of Child Behaviour checklist
Change in neuropsychology Brief
composite score of Brief
Change in neuropsychology Amsterdamse neuropsychologische test
composite score of Amsterdamse Neuropsychologische test (ANT)
Change in Insulin
insulin
Change in IGF1
IGF-1
Change in IGFPB3
IGFBP3
Change in pupillometry
dynamic pupillometry with infrared camera
Full Information
NCT ID
NCT02640443
First Posted
October 7, 2015
Last Updated
December 22, 2015
Sponsor
Universitair Ziekenhuis Brussel
Collaborators
KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT02640443
Brief Title
Sulfamethoxazole for the Treatment of Primary PREPL Deficiency
Acronym
SPPD
Official Title
Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Unknown status
Study Start Date
October 2015 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
October 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitair Ziekenhuis Brussel
Collaborators
KU Leuven
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypotonia Cystinuria Syndrome, Isolated PREPL Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
Outcomes Assessor
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Treatment with sulfamethoxazole. Subjects will serve as their own control, by using the data from baseline and after treatment stop.
Intervention Type
Drug
Intervention Name(s)
Sulfamethoxazole
Intervention Description
60 mg sulfamethoxazole per kg bodyweight (maximal of 3g) divided in 2 doses per day during 3 weeks
Primary Outcome Measure Information:
Title
Change in ptosis on myasthenia gravis composite scale
Description
ptosis item on the myasthenia gravis composite scale: single blinded scoring on video-images
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in ptosis index
Description
ptosis index, single blinded measurement on photograph
Time Frame
Change in index between baseline/1 week after treatment stop versus third week of treatment
Title
Change in lip length index
Description
lip length index, single blinded measurement on photographs
Time Frame
Change in index between baseline/1 week after treatment stop versus third week of treatment
Title
Change in lip purse index
Description
Lip purse index, single blinded measurement on photographs
Time Frame
Change in index between baseline/1 week after treatment stop versus third week of treatment
Secondary Outcome Measure Information:
Title
Change in satiety
Description
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)
Time Frame
Change in Composite score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in myasthenia gravis composite score
Description
Sum of all the subscores
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
myasthenia gravis composite dysarthria and eye closure subscores
Description
scored on video
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in muscle strength
Description
scored with hand-held manometry
Time Frame
Change in strength between baseline/1 week after treatment stop versus third week of treatment
Title
Change in complete blood count
Description
complete blood count (development of cytopenia)
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
Title
Change in Glycemia
Description
Glycemia
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
Title
Change in renal ultrasound
Description
renal ultrasound
Time Frame
development of kidney stones after the third week of treatment versus baseline
Title
Change in myasthenia gravis-activities of daily life
Description
Scale with rating of activities of daily life
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in neuropsychology Child Behaviour checklist
Description
composite score of Child Behaviour checklist
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in neuropsychology Brief
Description
composite score of Brief
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in neuropsychology Amsterdamse neuropsychologische test
Description
composite score of Amsterdamse Neuropsychologische test (ANT)
Time Frame
Change in score between baseline/1 week after treatment stop versus third week of treatment
Title
Change in Insulin
Description
insulin
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
Title
Change in IGF1
Description
IGF-1
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
Title
Change in IGFPB3
Description
IGFBP3
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
Title
Change in pupillometry
Description
dynamic pupillometry with infrared camera
Time Frame
Change between baseline/1 week after treatment stop versus third week of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Months
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luc Régal, MD
Organizational Affiliation
Universitair Ziekenhuis Brussel
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
24610330
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.
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Sulfamethoxazole for the Treatment of Primary PREPL Deficiency
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