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Intracerebroventricular 2-Hydroxypropyl-B-Cyclodextrin in Patients with Niemann-Pick Disease, Type C1
This study is currently recruiting participants.
Summary | Eligibility | Citations | Contacts
Summary
Number |
13-CH-0001 |
Sponsoring Institute |
National Institute of Child Health and Human Development (NICHD) |
Recruitment Detail |
Type: Participants currently recruited/enrolled |
Referral Letter Required |
No |
Population Exclusion(s) |
None |
Special Instructions |
Currently Not Provided |
Keywords |
Niemann-Pick Disease, Type C1; |
Recruitment Keyword(s) |
None |
Condition(s) |
Niemann-Pick Disease, Type C1 |
Investigational Drug(s) |
2-hydroxypropyl-beta-cyclodextrin |
Investigational Device(s) |
None |
Intervention(s) |
Drug: 2-hydroxypropyl-beta-cyclodextrin |
Supporting Site |
|
- 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 7 and 25 years of age who have been diagnosed with 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 an Ommaya reservoir placed under the scalp to allow the drug to be given into a cavity of the brain for treatment. This will require surgery. A brain scan will be performed to help place the equipment.
- Participants will receive doses of HPBCD through the Ommaya reservoir. They will receive one dose of HPBCD once a month. The length of the trial will be determined by the safety and efficacy information we obtain.
- Treatment will be monitored with frequent blood and urine tests, Cerebral Spinal Fluid tests, and neurological exams.
Eligibility
INCLUSION CRITERIA:
1. Aged greater than or equal to 7 and less than or equal to 25 years old at time of enrollment, either gender and any ethnicity.
2. Diagnosis of NPC1 based upon one of the following:
a. Two NPC1 mutations;
b. Positive filipin staining and at least one NPC1 mutation;
c. Vertical supranuclear gaze palsy (VSNGP) in combination with either:
i. One NPC1 mutation, or
ii. Positive filipin staining and no NPC2 mutations.
3. 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.
4. Ability to travel to the NIH CC repeatedly for evaluation and follow-up.
5. 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.
6. Willing to discontinue all non-prescription supplements, with the exception of an age-appropriate multivitamin.
7. Women of reproductive age must be willing to use an effective method of contraception for the duration of the trial.
8. Willing to undergo placement of an Ommaya reservoir for administration of an experimental drug.
9. Willing to participate in all aspects of trial design including serial blood and CSF collections.
EXCLUSION CRITERIA:
1. Aged below 7 or above 25 years of age at enrollment in the trial.
2. Weight less than 10 kg.
3. Severe manifestations of NPC1 that would interfere with the patient's ability to comply with the requirements of this protocol.
4. Neurologically asymptomatic patients.
5. 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.
6. History of hypersensitivity reactions to cyclodextrin or components of the formulation.
7. Pregnancy or breastfeeding at any time during the study.
8. Patients with suspected infection of the CNS or any systemic infection.
9. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1,500.
10. Thrombocytopenia (a platelet count of less than 75,000 per cubic millimeter).
11. Evidence of disturbed circulation of CSF.
12. Contraindication to placement of an Ommaya reservoir or anesthesia.
13. Prior use of anticoagulants or history/presence of a bleeding disorder.
14. Hepatic laboratory parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT],) greater than 4-times upper limit of normal.
15. Presence of anemia defined as two standard deviations below normal for age and gender.
16. Serum creatinine level greater than 1.5 times the upper limit of normal.
17. Hematuria on a single urinalysis, as defined by the American Urological Association (AUA) as five or more red blood cells per high-power field (or > 25/micro L) on microscopic evaluation of urinary sediment from a properly collected urinalysis specimen. The patient will not be excluded if 2 subsequent urine specimens are negative for hematuria as defined by the AUA.
18. Proteinuria (1+ protein on urinalysis) unless evaluated and classified as benign by patient's primary medical provider.
19. Active pulmonary disease, oxygen requirement or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
20. Patients unable to complete a behavioral audiologic evaluation including pure-tone threshold assessment (500 Hz to 8000 Hz) to monitor for ototoxicity.
21. Patients with uncontrolled seizures, specifically: greater than 1 seizure over a 2-month period (quantified over the 6 months prior to enrollment), patients requiring antiepileptic medication changes (other than dose adjustment for weight) in the 6 months prior to enrollment), or requiring 2 or more antiepileptic medications to control seizures.
22. Patients, who in the opinion of the investigators are unable to comply with the protocol or have specific health concerns that would potentially increase the risk of participation.
Citations:
Contacts:
Principal Investigator |
Referral Contact |
For more information: |
| Forbes D. Porter, M.D. National Institute of Child Health and Human Development (NICHD) National Institutes of Health BG 10-CRC RM 5-2571 MSC 1832 10 CENTER DR BETHESDA MD 20892-1832 (301) 435-4432 fdporter@mail.nih.gov |
Nicole M. Yanjanin, C.R.N.P. National Institute of Child Health and Human Development (NICHD) National Institutes of Health BG 10-CRC RM 1-3330 MSC 1103 10 CENTER DR BETHESDA MD 20892-1103 (301) 594-1765 nyanjanin@mail.nih.gov |
Patient Recruitment and Public Liaison Office Building 61 10 Cloister Court Bethesda, Maryland 20892-4754 Toll Free: 1-800-411-1222 TTY: 301-594-9774 (local),1-866-411-1010 (toll free) Fax: 301-480-9793 prpl@mail.cc.nih.gov |
Clinical Trials Number:
NCT01747135
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