NGLY1 Deficiency
Conditions
Brief summary
In patients with NGLY1-CDDG, the disorder can lead to eye damage due to not being able to produce enough tears. This study is being done to see if the dietary supplement, GlcNAc, improves tear production in patients with NGLY1-CDDG.
Detailed description
This study is a multicenter randomized, double-blind, placebo-controlled trial of GlcNAc supplementation for improvement of tear production in NGLY1-CDDG. Clinical history and screening data will be reviewed to determine subject eligibility. If a subject is already on GlcNAc, a washout period of 1 month will be required prior to consent and randomization. Interested subjects who have a molecularly confirmed diagnosis of NGLY1-CDDG will be consented. Baseline data will be collected prior to randomization at treatment initiation. Subjects will then be randomized to placebo or GlcNAc. They will be administered weight-dependent doses of GlcNAc or an equivalent volume of placebo enterally for 6 weeks, followed by open label weight-dependent doses of GlcNAc for 6 weeks. A visit for evaluation and collection of lab samples will be conducted at 6 and 12 weeks.
Interventions
DRUGGlcNAc-GlcN
GlcNAc powder - weight-dependent dose
OTHERPlacebo
Placebo xylose
Sponsors
Children's Hospital of Philadelphia
Seattle Children's Hospital
Eva Morava-Kozicz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Previously molecularly confirmed NGLY1-CDDG * Between the ages of 1 year old to 60 years old * Parent or legal guardian available to provide consent on behalf of minor subjects or adult subjects who are unable to give informed consent due to developmental disabilities. Willingness of subject or legal guardian to provide consent. * Non-pregnant, non-lactating female subjects of childbearing potential who are heterosexually active must agree to use a highly effective method of contraception for the duration of the study. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as oral/injectable/inserted/implanted/transdermal contraceptives, condom with diaphragm, condom with spermicide, diaphragm with spermicide, intrauterine hormone- releasing system, or intrauterine device (IUD), or sexual abstinence. Contraception is not required where at least 6 weeks have passed since sterilization, defined as females having undergone one of the following surgeries: hysterectomy, bilateral tubal ligation or occlusion, bilateral oophorectomy, or bilateral salpingectomy; and males who are vasectomized. Contraception is not required where females are postmenopausal (defined as 12 consecutive months of spontaneous amenorrhea and age ≥51 years)..
Exclusion criteria
* Hypersensitivity to any of the components of the placebo * History of treatment with GlcNAc within 28 days of Visit 1 * Participation in another therapeutic trial - the subject will not be permitted to participate in any other drug trial during the blinded phase and during the 28 days prior to Visit 1 * Shellfish allergy * Planned eye surgery within 3 months of enrollment * • Females that are pregnant, nursing or less than 6 months postpartum or attempting to conceive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in tear production from baseline in placebo vs GlcNAc group | 6 weeks | The primary endpoint of the study is the difference in tear production from baseline in individuals with NGLY1-CDDG between the placebo and the GlcNAc group after 6 weeks of blinded therapy, as measured by Schirmer II test which is a tool that helps assess the amount of tears in the eyes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of eye redness needing treatments | 6 weeks, 12 weeks | Patient/family reported frequency of eye redness after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
| Frequency of eye tearing/watering | 6 weeks, 12 weeks | Patient/family reported frequency of eye tearing/watering after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
| Frequency of eye infections needing treatments | 6 weeks, 12 weeks | Patient/family reported number of eye infections needing treatment in last month after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
| Frequency of wind sensitivity | 6 weeks, 12 weeks | Patient/family reported frequency of wind sensitivity after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
| Difference in tear production from baseline | 12 weeks | Difference in tear production, as measured by Schirmer II test, at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
| Frequency of light sensitivity | 6 weeks, 12 weeks | Patient/family reported frequency of light sensitivity after 6 weeks of blinded therapy and at 12 weeks after 6 weeks of open-label administration of GlcNAc. |
Countries
United States
Outcome results
None listed