Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00028262
Status:
COMPLETED
Last Update Posted:
2016-10-27
First Post:
2001-12-17
Brief Title:
Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis
Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Combination Therapy With Cystagon and N-Acetylcysteine for INCL Patients
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the effectiveness of a drug called Cystagon in treating infantile neuronal ceroid lipofuscinosis INCL a progressive neurological disease affecting children At around 11 to 13 months of age patients develop slowed head growth mild brain atrophy wasting electroencephalographic EEG changes and retinal deterioration with symptoms worsening over time The disease results from an enzyme deficiency that causes fatty compounds called ceroid to accumulate in cells In laboratory experiments Cystagon has helped remove ceroid from cells of patients with INCL
Children with INCL between 6 months and 3 years of age may be eligible for this study Participants take Cystagon daily by mouth every 6 hours They are admitted to the NIH Clinical Center for a 4- to 5-day period every 6 months for the following tests and evaluations
Review of medical history including a detailed record of seizures physical examination blood tests and clinical photographs For the initial baseline studies examinations may also be scheduled with pediatric neurology ophthalmology and anesthesia services
Magnetic resonance imaging MRI of the brain MRI uses a powerful magnet radio waves and computers to provide detailed images of the brain without the use of X-rays The patient lies on a table that slides inside a donut-shaped machine containing a magnetic field The child requires general anesthesia for the procedure
Electroretinogram ERG measures the function of the retina the light-sensitive tissue in the back of the eye To record the flash ERG a special contact lens is placed on the eye s surface and the eye is stimulated with flashes of light Infants and very young children require general anesthesia for the procedure
Visual evoked potential VEP measures the function of the visual pathway from the eye to the brain To record the VEP five electrodes are placed on the scalp and the eye is stimulated with flashes of light Infants and very young children must be anesthetized for the procedure
Electroencephalogram EEG measures brain electrical activity using electrodes placed on the scalp The test is useful in defining seizures The child may need to be sedated to keep still during the test
Skin biopsy A small piece of skin is removed usually from the upper arm or shoulder under local anesthetic to grow cells in the laboratory This procedure is done at the start of the study and is repeated after 1 year if therapy results are promising
Children s condition may improve stabilize or worsen during this study Life may be prolonged without significant improvement in quality The information gained from the study may help scientists develop more potent drugs to treat INCL
Children with INCL between 6 months and 3 years of age may be eligible for this study Participants take Cystagon daily by mouth every 6 hours They are admitted to the NIH Clinical Center for a 4- to 5-day period every 6 months for the following tests and evaluations
Review of medical history including a detailed record of seizures physical examination blood tests and clinical photographs For the initial baseline studies examinations may also be scheduled with pediatric neurology ophthalmology and anesthesia services
Magnetic resonance imaging MRI of the brain MRI uses a powerful magnet radio waves and computers to provide detailed images of the brain without the use of X-rays The patient lies on a table that slides inside a donut-shaped machine containing a magnetic field The child requires general anesthesia for the procedure
Electroretinogram ERG measures the function of the retina the light-sensitive tissue in the back of the eye To record the flash ERG a special contact lens is placed on the eye s surface and the eye is stimulated with flashes of light Infants and very young children require general anesthesia for the procedure
Visual evoked potential VEP measures the function of the visual pathway from the eye to the brain To record the VEP five electrodes are placed on the scalp and the eye is stimulated with flashes of light Infants and very young children must be anesthetized for the procedure
Electroencephalogram EEG measures brain electrical activity using electrodes placed on the scalp The test is useful in defining seizures The child may need to be sedated to keep still during the test
Skin biopsy A small piece of skin is removed usually from the upper arm or shoulder under local anesthetic to grow cells in the laboratory This procedure is done at the start of the study and is repeated after 1 year if therapy results are promising
Children s condition may improve stabilize or worsen during this study Life may be prolonged without significant improvement in quality The information gained from the study may help scientists develop more potent drugs to treat INCL
Detailed Description:
Neuronal ceroid lipofuscinoses NCLs commonly known as Batten disease represent a group of the most common 1 in 12500 heritable neurodegenerative storage disorders of childhood Mutations of at least 8 different genes are responsible for various forms of NCL The infantile form of NCL or INCL is the most severe disease It is caused by mutations in the palmitoyl-protein thioesterase-1 PPT1 gene PPT1 is a lysosomal enzyme that cleaves thioester linkages in S-acylated proteins and its deficiency leads to abnormal lysosomal accumulation of fattyacylated- proteins ceroids leading to INCL pathogenesis Since thioester linkages are labile drugs with nucleophilic property are likely to mimic PPT1 and may have therapeutic potential for INCL We previously reported that cysteamine phosphocysteamine cysteamine bitartrate cystagon and N-acetylcysteine disrupt thioester linkages in a model PPT1-substrate C14 palmitoyl-CoA releasing C14 palmitic acid The results of our laboratory studies have shown that cysteamine mediates the depletion of intracellular ceroid deposits and prevents their reaccumulation For the last 9 years we have been conducting a clinical trial to determine whether a combination of Cystagon Cysteamine bitartrate and N-acetylcysteine mucomyst is beneficial for INCL patients In parallel with these studies using an animal model of INCL we found that this combination therapy reduces oxidative stress caused by high levels of reactive oxygen species ROS in the brain of mice lacking the PPT1 enzyme To date we have admitted a total of 10 patients 5 females and 5 males to this protocol however one male patient was lost to follow-up Thus we have treated 9 patients 5 females and 4 males and these patients showed no adverse reactions to these drugs except for one patient who initially had mild gastrointestinal discomfort which went away when cystagon was stopped and restarted from the lowest dose and this mild adverse effect did not recur Compared with the published natural history of INCL our preliminary results show that although several parameters of disease progression are slowed due to the treatment it does not completely arrest the neurodegenerative process We are currently analyzing all the data gathered so far and a manuscript describing the results will be prepared for submission to a peer-reviewed journal
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-CH-0086 | None | None | None |