Congenital Disorders of Glycosylation
Conditions
Keywords
Glycosylation, Glucose Metabolic Disorder, Galactose
Brief summary
The goal of this study is to better characterize the metabolic alterations and sugar structure alterations (glycosylation abnormalities) in patients diagnosed with Congenital Disorders of Glycosylation. The investigators aim to assess the safety and tolerability of oral galactose treatment in a small pilot group of Congenital Disorders of Glycosylation patients. The investigators will also determine the relationship between simple milk sugar intake (galactose dose) in the diet and the blood and urine markers of protein glycosylation abnormalities.
Detailed description
The primary hypothesis in this study is that adding simple milk sugar (galactose) to the diet of Congenital Disorders of Glycosylation patients will normalize the metabolic abnormalities. The secondary hypothesis posits that galactose intervention in Congenital Disorders of Glycosylation patients will normalize specific physiological biomarkers of protein glycosylation that can be utilized for future phase II/III trial development. The knowledge gained from the investigation of these two aims will help the investigators learn more about the disrupted metabolic mechanism of this disease and should lead to the identification of new disease biomarkers that can be used to evaluate clinical efficacy in future therapeutic trials. Over a two-year period, the investigators will enroll patients diagnosed with Congenital Disorders of Glycosylation. The investigators propose to administer oral galactose supplementation for a period of 18 weeks in increasing dose to assess its effectiveness at normalizing glycosylation. Galactose will be given in a series of doses within the range of normal dietary intake of galactose over fixed time points. To assess the effects of oral galactose supplementation for each participant, changes in participant growth, as well as blood sugar levels, coagulation parameters and liver function (the primary clinical features of Congenital Disorders of Glycosylation) will be correlated with biomarkers derived from participant blood and urine samples obtained at key time points and then compared to standard normative ranges of data for each measure.
Interventions
DIETARY_SUPPLEMENTD-Galactose
D-Galactose is an oral powdered dietary supplement to be taken by mouth.
Sponsors
Tulane University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dietary Supplement: D-Galactose
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* Biochemically and genetically proven Congenital Disorders of Glycosylation.
Exclusion criteria
* Any of the following conditions: * Aldolase B Deficiency * Galactosemia (unable to process galactose) * Hemolytic uremic syndrome * Severe anemia * Diagnosis of intellectual disability or developmental delay * Galactose Intolerance * Has previously experienced any of the following severe side effects from oral galactose: * Diarrhea * Vomiting * Constipation * Galactosuria (Galactose in the urine) * Increased liver glycogen storage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Function | 18 weeks | Assess if the introduction of galactose into the subject's diet will normalization metabolic function. Metabolic function will be based on liver function and used for muscle enzyme tests, thyroid and growth hormone measurement, coagulation and anti-coagulation factors, blood sugar and milk-acid and biochemical/metabolic parameters. These measurements will be assessed together to see how many subjects will remain with abnormal values or change to within normal levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers for protein glycosylation | 18 weeks | Identify potential biomarkers for glycosylation and metabolic dysfunction. And learn the physiological effect of adding galactose to the diet on known biomarkers for protein glycosylation. Specific biomarkers that will be examined include: transferrin glyco isoforms, antithrombin III, coagulation factor IX and XI, IGFBP3 and TSH. These measurements will be assessed together to see how many subjects will remain with abnormal values or change to within normal levels. |
Countries
United States
Outcome results
None listed