Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00028262
• Date of registration: 17/12/2001
• Prospective Registration: No
• Primary sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Public title: Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis
• Scientific title: A Combination Therapy With Cystagon and N-Acetylcysteine for INCL Patients
• Date of first enrolment: February 2001
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00028262
• Study type: Interventional
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Anil B Mukherjee, M.D.
• Affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Key inclusion & exclusion criteria

- INCLUSION and EXCLUSION CRITERIA:

Only patients between 6 months and 3 years of age will be admitted in this study. Parents
or caregivers of patients recruited to the study will be provided with a copy of the
protocol and the consent form to review prior to their coming to the NIH. They will be
encouraged to call either Dr. Levin or Dr. Mukherjee to discuss any questions they may have
concerning the protocol prior to enrollment in the study.

The proposed age range (6 mo to 3 yrs) was chosen because these children are expected to
have a mild to moderate neurological deficiency but are well enough to be cared for at home
by the family. Therefore, these patients should not require extensive medical or nursing
care during their stay at the Clinical Center. Moreover, the patients are locally cared for
by neurologists and pediatricians on a regular basis, and such care will continue when the
patients return home.

The rigid age exclusion criteria will be used because the majority of INCL patients have
more frequent seizures, complete retinal blindness and significant cerebral atrophy beyond
3 years of age. Dr. Santavuori (one of our consultants who is now deceased), who had the
most extensive experience with these patients, believed that the neurological degeneration
after age 2 might not be reversible. While Dr. Santavuori s speculation is well taken, we
feel that since to date there has not been any effective treatment to slow the progression
of neuronal death in INCL, and since our preliminary results show that Cystagon slows the
progression of neurodegeneration, we feel that a combination of Cystagon plus N-Ac with its
anti-apoptotic and neuro-protective effects may show some added benefits over Cystagon
therapy alone.

In our initial protocol we restricted the admission of patients that carried two lethal
mutations in the PPT1 gene. The purpose of including only those patients who carry specific
PPT1 mutations

(L10X, R151X, R164X, W296X, R122W, c.169insA and E184K) was to establish that the
beneficial effects of the combination therapy because a patients who had any two of these
mutations manifested the most severe disease phenotype. Because of the uniform
manifestation of the disease it was easier to determine any beneficial effects of the
combination drug therapy.

Subsequently, our protocol was approved for treatment of INCL patients with any two
mutations in the PPT1 gene. Our protocol has been previously amended to include all INCL
patients regardless of the PPT1 mutations they carry.

Patients with intractable seizures that cannot be controlled by two or fewer antiepileptic
medications will not be accepted for this study. Patients who cannot take nourishment
orally or who are in a vegetative state will not be enrolled in this study even if the 6
months to 3 year age criterion is met.

Both male and female patients are eligible for enrollment in this study.



Age minimum: 6 Months
Age maximum: 3 Years
Gender: All

Health Condition(s) or Problem(s) studied

Infantile Neronal Ceroid Lipofuscinosis

Intervention(s)

Drug: Cystagon

Primary Outcome(s)

Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells. [Time Frame: 10 years]

Secondary ID(s)

010086

01-CH-0086

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/01/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00028262