Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease
1 other identifier
interventional
14
1 country
1
Brief Summary
Background: \- Hydroxypropyl beta cyclodextrin (HPBCD) is being tested for a disease called Niemann-Pick disease type C1 (NPC1). NPC1 is a genetic disorder that results in gradual loss of nervous system function. Cholesterol and other fats have trouble moving out of the brain cells, which makes the cells work poorly and leads to symptoms. There is no treatment currently approved in the US for NPC1. Researchers want to test if it is safe to use HPBCD for NPC1. They want to see if it can help brain cells process cholesterol better. Objectives: \- To test the safety and effectiveness of HPBCD for NPC1. Eligibility: \- Individuals between 2 and 25 years of age who have been diagnosed with NPC1 and who have not already received HPBCD in an attempt to treat NPC1. Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples for screening. They will also have neurological tests, including tests of hearing, speech and movement.
- Participants will have a lumbar puncture (also called a spinal tap) every month to deliver the drug to the spinal fluid that surrounds the brain. The length of the trial will be determined by the safety and efficacy information that is obtained.
- Treatment will be monitored with frequent blood and urine tests, cerebral spinal fluid tests, hearing and neurological exams.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2013
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 8, 2012
CompletedFirst Posted
Study publicly available on registry
December 11, 2012
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2017
CompletedJuly 23, 2021
July 1, 2021
4.2 years
December 8, 2012
July 19, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
24-hydroxycholesterol Area under the curve
Days
Secondary Outcomes (1)
Hearing loss.
Year
Study Arms (1)
Open label
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- Aged greater than or equal to 2 and less than or equal to 25 years old at time of enrollment, either gender and any ethnicity.
- Diagnosis of NPC1 based upon one of the following:
- Two NPC1 mutations;
- Positive filipin staining and at least one NPC1 mutation;
- Vertical supranuclear gaze palsy (VSNGP) in combination with either:
- i. One NPC1 mutation, or
- ii. Positive filipin staining and no Niemann-Pick Type 2 (NPC2) mutations.
- Patients with at least one neurological manifestation of NPC1. For example, but not limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia, dystonia, seizures, dysarthria, or dysphagia.
- Ability to travel to the National Institutes of Health Clinical Center (NIH CC) repeatedly for evaluation and follow-up.
- If taking miglustat, the patient must have been taking a constant dose of the medication for no less than 3 months prior to baseline evaluation and must be willing to maintain that dose level for the duration of the trial.
- Willing to discontinue all non-prescription supplements, with the exception of an age-appropriate multivitamin.
- Women of reproductive age must be willing to use an effective method of contraception for the duration of the trial.
- Willing to participate in all aspects of trial design including serial blood and cerebrospinal fluid (CSF) collections.
You may not qualify if:
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- Aged below 2 or above 25 years of age at enrollment in the trial.
- Subjects will be excluded if their weight would result in an endotoxin level that would exceed 0.2 EU/kg for either the saline or drug dosing.
- Severe manifestations of NPC1 that would interfere with the patient's ability to comply with the requirements of this protocol.
- Neurologically asymptomatic patients.
- Patients who have received any form of cyclodextrin in an attempt to treat NPC1. Treatment with another drug preparation for another medical indication that contains cyclodextrin as an excipient, will not exclude a patient.
- History of hypersensitivity reactions to cyclodextrin or components of the formulation.
- Pregnancy or breastfeeding at any time during the study.
- Patients with suspected infection of the CNS or any systemic infection.
- Spinal deformity that would impact the ability to perform a lumbar puncture
- Skin infection in the lumbar region
- Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1,500.
- Thrombocytopenia (a platelet count of less than 75,000 per cubic millimeter).
- Evidence of disturbed circulation of CSF.
- Contraindication for anesthesia.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (6)
Aqul A, Liu B, Ramirez CM, Pieper AA, Estill SJ, Burns DK, Liu B, Repa JJ, Turley SD, Dietschy JM. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci. 2011 Jun 22;31(25):9404-13. doi: 10.1523/JNEUROSCI.1317-11.2011.
PMID: 21697390BACKGROUNDBrewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007 Jul 30;59(7):645-66. doi: 10.1016/j.addr.2007.05.012. Epub 2007 May 29.
PMID: 17601630BACKGROUNDChen FW, Li C, Ioannou YA. Cyclodextrin induces calcium-dependent lysosomal exocytosis. PLoS One. 2010 Nov 29;5(11):e15054. doi: 10.1371/journal.pone.0015054.
PMID: 21124786BACKGROUNDFarmer C, Lewis M, Farhat N, Robbins KP, Joseph L, Albert OK, Bianconi S, Hoffmann A, Giserman-Kiss I, Alexander DM, Thurm A, Porter FD, Kravis EB. Convergent Validity of the Fine Motor, Speech, and Cognitive Domains of the 5-Domain Niemann-Pick Disease Type C Clinical Severity Scale. J Child Neurol. 2026 Jan;41(1):43-53. doi: 10.1177/08830738251346348. Epub 2025 Jun 17.
PMID: 40525490DERIVEDBoenzi S, Catesini G, Sacchetti E, Tagliaferri F, Dionisi-Vici C, Deodato F. Comprehensive-targeted lipidomic analysis in Niemann-Pick C disease. Mol Genet Metab. 2021 Dec;134(4):337-343. doi: 10.1016/j.ymgme.2021.11.005. Epub 2021 Nov 16.
PMID: 34810067DERIVEDFarmer CA, Thurm A, Farhat N, Bianconi S, Keener LA, Porter FD. Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-beta-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1. CNS Drugs. 2019 Jul;33(7):677-683. doi: 10.1007/s40263-019-00642-2.
PMID: 31187454DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Global Clinical Leader
Mallinckrodt
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2012
First Posted
December 11, 2012
Study Start
January 1, 2013
Primary Completion
March 1, 2017
Study Completion
March 1, 2017
Last Updated
July 23, 2021
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will not share
Publish in peer reviewed journal