a prospective non-therapeutic study in patients diagnosed with niemann-pick disease type c

Conditions: Niemann-Pick Disease, Type C

Summary: this is a prospective non-therapeutic observational study in np-c patients. the aim is to characterize the individual patient disease progression profile through the historical and 6 months prospective evaluation of clinical, imaging, biological(biomarkers) and quality of life data. patients will be offered enrollment into a phase ii/iii study on arimoclomol at the end of the study.


Eligibility criteria:
inclusion criteria: * written informed consent (and assent if appropriate to local laws and regulations) prior to any study-related procedures; * males and females aged from 2 years to 18 years and 11 months; * patients of any ethnic background will be eligible for this study; * patient weight ≥15th percentile of body mass index (bmi) for age according to the world health organisation (who) standards; * diagnosis of niemann pick disease type c (np-c), either npc1 or npc2; * np-c diagnosis genetically confirmed (deoxyribonucleic acid \[dna\] sequence analysis); * both npc1 and npc2 patients are eligible; * presenting at least one neurological symptom of the disease (for example, but not limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia, dystonia, seizures, dysarthria, or dysphagia); * ability to walk either independently or with assistance; * ability to travel to the corresponding clinical trial site repeatedly (every 6 months) for evaluation and follow-up; * treated or non-treated with miglustat; * if a patient is under prescribed treatment with miglustat, it has to be under stable dose of the medication for ≥ 3 continuous months prior to inclusion in the study; * sexually active patients must be willing and able to use an adequate method of contraception throughout the study, for example: diaphragm + spermicide; intrauterine contraceptive device; oral contraceptives; implant; injection of a progestogen medication; * ability to comply with the protocol-specified procedures/evaluations and scheduled visits; * willing to participate in all aspects of trial design including serial blood sampling, skin biopsies and imaging (ultrasonography) collections. exclusion criteria: * no written informed consent obtained from the patient or their parent(s)/legal guardian(s) (and assent if appropriate to local laws and regulation) before any study related procedures; * recipient of a liver transplant or planned liver transplantation; * patients with uncontrolled severe epileptic seizures period (at least 3 consecutive severe epileptic seizures that required medication) within 2 months prior to the written consent. this includes patients with ongoing seizures that are not stable in frequency or type or duration over a 2 month period prior to enrollment, requiring change in dose of antiepileptic medication (other than adjustment for weight) over a 2 month period prior to enrollment, or requiring 3 or more antiepileptic medications to control seizures; * neurologically asymptomatic patients; * severe liver insufficiency (defined as hepatic laboratory parameters, aspartate transaminase \[ast\] and alanine transaminase \[alt\] greater than three-times the upper limit of normal for age and gender; * severe renal insufficiency, with serum creatinine level greater than 1.5 times the upper limit of normal ; * severe manifestations of np-c disease that would interfere with the patient's ability to comply with the requirements of this protocol; * in the opinion of the investigator, the patient's clinical condition does not allow for the required blood collection and/or skin biopsies as per the protocol-specified procedures; * treatment with any imp within 4 weeks prior to the study enrollment; * treatment with any imp during the study in an attempt to treat np-c; * current participation in another trial is not permitted unless it is a non-interventional study and the sole purpose of the trial is for long-term follow up/survival data (registry); * patients will be excluded if there is a confirmed risk linked to the mri procedure to be performed in the subsequent therapeutic interventional study \[i.e.: implanted cardiac pacemaker or implantable cardioverter defibrillator, implanted neural pacemakers, cochlear implants, implanted metallic foreign bodies in the eye or cns (such as a cns aneurysmal clip), any form of implanted wire or metal device that may concentrate radio frequency fields and/or confirmed history of unexpected serious adverse reaction to sedation or anesthesia (if sedation is necessary)\]; * patients will be excluded if there is a confirmed risk linked to the skin punch biopsy procedure like severe thrombocytopaenia, at investigator's discretion.

Keywords: np-c lsd lysosomal storage disorder lysosomal storage disease npc2 npc1 niemann-pick type c niemann-pick, arimoclomol