E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypotonia-cystinuria syndrome and isolated PREPL deficiency. |
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E.1.1.1 | Medical condition in easily understood language |
Hypotonia-cystinuria syndrome and isolated PREPL deficiency. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of therapeutic effect of sulfamethoxazole in patients with primary PREPL deficiency (hypotonia-cystinuria syndrome or isolated PREPL deficiency). These syndromes are characterized by severe neonatal hypotonia, which improves spontaneously. However, ptosis, dysarthria, facial weakness and mild proximal weakness persist. We want to evaluate the effects on these neuromuscular symptoms systematically, as we observed improvement during treatment with sulfamethoxazole-trimethoprim. As sulfamethoxazole has sulfonylurea side effects, it is the best candidate to explain this therapeutic effect. |
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E.2.2 | Secondary objectives of the trial |
Evaluation of therapeutic effect of sulfamethoxazole in patients with primary PREPL deficiency on non-neuromuscular symptoms. These patients also have growth hormone deficiency, childhood overeating with obesity and variable cognitive difficulties. During the trial we will analyse neuropsychology, satiety and growth hormone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of hypotonia cystinuria syndrome or isolated PREPL deficiency by molecular genetics.
Able to be compliant with the study protocol.
Not of childbearing age (women).
Children and adults.
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E.4 | Principal exclusion criteria |
Not able to comply with the study protocol
Women of childbearing age
Concomitant neuromuscular disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Ptosis evaluated with the MG composite, single blinded (videotape)
Ptosis evaluated with ptosis index (photograph, single blinded)
Facial weakness evaluated with lip length and snout index
Comparison between baseline and treatment and between treatment and stop of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After three weeks of treatment. (Baseline of 7 days, posttreatment of 7 days) |
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E.5.2 | Secondary end point(s) |
Myasthenia gravis composite, myasthenia gravis composite dysarthria score, myasthenia gravis composite eye closure score, muscle force (manual dynamometry)
MG-ADL, Neuropsychological tests: Amsterdamse test, CBCL, BRIEF.
Blood measures: Complete blood count, glycemia, IGF-1, insulin, IGFBP3 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Also after 3weeks of treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Baseline-treatment-stop (1w-3w-1w) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |