Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease

This study is currently recruiting participants.
Verified September 2012 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
First received: December 8, 2012
Last updated: January 31, 2013
Last verified: September 2012


- 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.


- To test the safety and effectiveness of HPBCD for NPC1.


- Individuals between 7 and 25 years of age who have been diagnosed with NPC1.


  • 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.

Condition Intervention Phase
Niemann-Pick Disease, Type C1
Drug: 2-hydroxypropyl-beta-cyclodextrin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intracerebroventricular 2-Hydroxypropyl-B-Cyclodextrin in Patients With Niemann-Pick Disease, Type C1

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 24-hydroxycholesterol Area under the curve [ Time Frame: Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hearing loss. [ Time Frame: Year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: November 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 2-hydroxypropyl-beta-cyclodextrin
Detailed Description:

Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). The National Institutes of Health (NIH) Therapeutics for Rare and Neglected Diseases (TRND) program is developing 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) for the treatment of patients with Niemann-Pick disease type C1 (NPC1) to slow progression of symptoms of the disease. In this Phase 1, non-randomized, open-label, single-center, study, we propose to administer HP-beta-CD intracerebroventricularly via an Ommaya reservoir to 3 cohorts of 3 patients at doses of 50 mg escalated to 100, 200, and 400 mg, in Cohorts 1, 2, & 3 respectively. The objectives of this study are to assess the safety, tolerability, feasibility, and pharmacokinetics (PK) of intracerebroventricular (ICV) administered HP-beta-CD to NPC1 patients, to determine an active dose of HP-beta-CD as measured by changes in plasma 24-(S) hydroxycholesterol (24-HC) levels, and to evaluate the use of biomarkers and potential clinical outcomes of NPC1. All patients in the cohort will receive HP-beta-CD (n = 3) once monthly for at least 2 doses, and the decision to dose-escalate will be based on safety and on biochemical data. Safety will be assessed by adverse events (AEs), audiologic evaluation, clinical laboratory tests, vital signs, physical examinations, chest X-rays and electrocardiograms (ECGs). Biochemical efficacy will be measured by change from baseline in plasma 24-HC. PK will be assessed for both cerebrospinal fluid (CSF) and plasma HP-beta-CD.


Ages Eligible for Study:   7 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

    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:

      1. Two NPC1 mutations;
      2. Positive filipin staining and at least one NPC1 mutation;
      3. 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.


  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 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01747135

Contact: Nicole M Yanjanin, C.R.N.P. (301) 594-1765 nyanjanin@mail.nih.gov
Contact: Forbes D Porter, M.D. (301) 435-4432 fdporter@mail.nih.gov

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)     800-411-1222 ext TTY8664111010     prpl@mail.cc.nih.gov    
Sponsors and Collaborators
Principal Investigator: Forbes D Porter, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT01747135     History of Changes
Other Study ID Numbers: 130001, 13-CH-0001
Study First Received: December 8, 2012
Last Updated: January 31, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Niemann-Pick Disease, Type C1

Additional relevant MeSH terms:
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations

ClinicalTrials.gov processed this record on February 11, 2013