Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine

Summary

Background:

* Niemann-Pick disease type C (NPC) is a genetic disorder that results in progressive loss of nervous system function by affecting the membranes of nerve cells. There is no known cure for NPC.
* N-acetyl cysteine (NAC) is a drug that has been approved by the Food and Drug Administration to use either orally or IV for the treatment of acetaminophen (Tylenol) poisoning or as an aerosol to reduce the stickiness of mucous in patients with cystic fibrosis. In the body, NAC is converted to an amino acid called cysteine, which cells can convert to a chemical called glutathione. Glutathione is important in helping cells deal with oxidative stress. Based on a number of experiments in cells, mice and patients with NPC, we believe that oxidative stress is increased in NPC. If we can increase glutathione levels, we may be able to decrease the oxidative stress.

Objectives:

\- To test the safety and effectiveness of N-acetyl cysteine to treat Niemann-Pick disease (type C).

Eligibility:

\- Individuals at least 1 year of age who have been diagnosed with NPC.

Design:

* Patients entering this study will be seen at the National Institutes of Health Clinical Center four times during the 20 weeks of the study. These admissions will occur at the start of the study and at weeks 8, 12, and 20. The first NIH visit will last 2 days, and the other visits will last 1 day.
* Patients will participate in a two-stage study: a period of 8 weeks receiving NAC and a second period of 8 weeks when receiving a placebo (a pill without NAC). Every patient participating in this study will receive NAC during one of the two time periods.
* The two treatment periods will be separated by a wash-out period, 4 weeks when patients will receive neither NAC nor placebo. Patients will also have a 4-week wash-out period at the beginning of the study. Most physician-prescribed medications, such as seizure medications, will be allowed.
* During each visit, examinations, procedures, and tests will be done, including blood and urine samples.

Conditions

• Niemann-Pick Disease, Type C

Interventions

DRUG

N-Acetyl Cysteine

900mg effervescent tablet; Dosed as 15 mg/kg/day (maximum dose 900 mg per day) for one week, advanced to 30 mg/kg/day (maximum dose 1800 mg per day) for the second week, and then advanced to 60 mg/kg/day (maximum dose 2700 mg) for the remainder of the trial (6 additional weeks).

Sponsors & Collaborators

• University of Oxford

  collaborator OTHER

• Washington University School of Medicine

  collaborator OTHER

• National Human Genome Research Institute (NHGRI)

  collaborator NIH

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  lead NIH

Principal Investigators

• Forbes D Porter, M.D. · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

12 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-08-31

Primary Completion

2010-11-30

Completion

2010-11-30

Countries

• United States

Study Locations