Immunologic Effects of Supplemental Monosaccharide and Nucleoside Derivatives in Patients With Inherited Disorders of Glycosylation

NCT02511041 | Terminated Phase 1

• 2 other identifiers: 15015915-I-0159
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- A congenital disorder of glycosylation (CDG) affects the cells that make up the organs and tissues. In these cells, sugar molecules do not properly attach to other molecules, which are the basic building blocks of cells. Changes in sugars seen in people with CDGs may lead to allergies and can change people s ability to fight infections. Researchers want to see if a sugar supplement called N-acetylglucosamine can help people with CDGs who have detectable changes in their immune systems. Objective: \- To see if N-acetylglucosamine can help cells to function in a healthy way in people with CDGs. Eligibility: \- People at least 2 years of age who have a CDG and immune system changes. Design:

• Participants will be screened with a physical exam, medical history, and blood tests.
• One month later, participants will repeat the blood tests from the screening visit. Blood will be drawn on 2 different days in the same week.
• Participants will get N-acetylglucosamine supplements and instructions for how to take them. N-acetylglucosamine is a powder that can be added to food or drink.
• Participants will have a physical exam and blood tests every month during the study.
• After taking N-acetylglucosamine for about 4 months, participants will have more blood tests. They will get more N-acetylglucosamine supplements and a nucleoside supplement. The second supplement may be a powder or tablets that may be crushed and added to food. Participants will take both supplements for 5 months.
• After about 10 months in the study, participants will have 2 more visits in the same week for the same blood tests.

Conditions

PGM3

Keywords

CDG; PGM3; Immune

Outcome Measures

Primary Outcomes (1)

• In patients with evidence of altered glycosylation and immunologic abnormalities, to assess the effects of oral monosaccharides and nucleosides on: a) Absolute lymphocyte count

  Monthly

Secondary Outcomes (1)

• To assess the effects of oral monosaccharides and nucleosides on: e) Serum and secreted immunoglobulin levels f) Lymphocyte subsets, function, proliferation, and apoptosis g) Innate immune function h) Glycosylation patterns of serum and cellular...

  Mid study Day 111 and end of study Day 252

Study Arms (1)

1

EXPERIMENTAL

This is a prospective exploratory study of nucleoside and monosaccharide supplement-ation and its effect on immunologic parameters in patients with evidence of altered glycosylation and immunologic abnormalities. Up to 50 subjects will receive escalating doses of oralmonosaccharide until a maximum tolerated dose is found and maintained for 6 weeks. Then nucleosidesupplementation will be added and the maximum tolerated dose will continue for 12 weeks. Parameters of interest will be assessed at NIH every 8 weeks. Themaximum participation time for each subject is 252 days. We will begin with PGM3 deficient patients, who will self-administer oral GlcNAc followed by dual supplementation with GlcNAc and Uridine. The remaining subjects will then receive these supplements following the same step-wise approach.

Drug: N-Acetylglucosamine (GlcNAc); Drug: Uridine

Interventions

N-Acetylglucosamine (GlcNAc) DRUG

N-acetylglucosamine (GlcNAc), 2-acetamino-2-deoxy- \<=-Dglucose, or 2- acetylamino)-2- deoxy-D-glucose, is a monosaccharide derivative of glucose. It is classified as dietary supplement in the United States. In general, it is a white and slightly sweet powder that melts at 221 degrees C. The solubility of GlcNAc is 25% in water, and 1% aqueous solutions are colorless and clear. GlcNAc is contraindicated for patients receiving warfarin, chemotherapy or diabetes drugs. As GlcNAc may interfere with blood sugar control during and after surgery, it is contraindicated during the two weeks prior to major surgery.

1

Uridine DRUG

Uridine 5 -monophosphate (UMP) disodium salt is a water soluble colorless crystalline powder which melts at 202oC.

1

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have:
• Age greater than or equal to 2 years
• An inherited syndrome presenting with immunologic abnormalities and altered glycosylation detected using clinical tests evaluating N- and O-linked glycan by mass spectroscopy
• A local physician who is willing to follow the patient during the study period
• For females of childbearing potential, willingness to use a highly effective method of contraception (e.g., abstinence, intrauterine device \[IUD\]; oral contraceptives; diaphragms; or condom in combination with contraceptive foam, jelly, or cream; Norplant, contraceptive patch or cervical ring)
• Willingness to have samples stored for future research including genetic testing

You may not qualify if:

• Pregnant, breastfeeding, or intent to become pregnant
• Renal failure or chronic kidney disease requiring dialysis
• Uncontrolled asthma
• Abuse of drugs or alcohol as assessed during complete history and physical performed at the screening visit
• Current or recent participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study
• Use of medications that interact with N-acetylglucosamine including warfarin and medications for the treatment of cancer (antimitotic chemotherapy including etoposide, teniposide, and doxorubicin) and diabetes (including glimepiride, glyburide, insulin, pioglitazone, rosiglitazone, chlorpropamide, glipizide and tolbutamide).
• Planned major surgery during the study period requiring general anesthesia
• Any condition that in the opinion of the investigator places the patient at undue risk for being in the study
• Unwillingness or inability to comply with the need to have periodic blood tests to monitor possible side effects of supplementation, or other major requirements of this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Davis SD, Schaller J, Wedgwood RJ. Job's Syndrome. Recurrent, "cold", staphylococcal abscesses. Lancet. 1966 May 7;1(7445):1013-5. doi: 10.1016/s0140-6736(66)90119-x. No abstract available.

  PMID: 4161105 BACKGROUND

• Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics. 1972 Jan;49(1):59-70. No abstract available.

  PMID: 5059313 BACKGROUND

• Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schaffer AA, Puck JM, Grimbacher B. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18;357(16):1608-19. doi: 10.1056/NEJMoa073687. Epub 2007 Sep 19.

  PMID: 17881745 BACKGROUND

MeSH Terms

Interventions

Acetylglucosamine; Uridine

Intervention Hierarchy (Ancestors)

Glucosamine; Hexosamines; Amino Sugars; Carbohydrates; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jonathan J Lyons, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: July 29, 2015
• Study Start: June 30, 2015
• Primary Completion: January 24, 2017
• Study Completion: January 24, 2017
• Last Updated: July 2, 2017

Record last verified: 2017-01-24

Locations

US (1)