NCT01634750

Phase I Clinical Trial of ManNAc in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy (HIBM)

Completed Phase 1 Last updated 19 October 2017

What this trial tests

Phase 1 trial testing ManNAc in Hereditary Inclusion Body Myopathy (HIBM) in 26 participants. Completed in 29 May 2013.

Timeline

11 September 2012

29 May 2013

Quick facts

Lead sponsor	National Human Genome Research Institute (NHGRI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	26
Start date	11 September 2012
Estimated completion	29 May 2013
Sites	1 location across United States

Drugs / interventions tested

• ManNAc — full drug profile →

Conditions studied

• Hereditary Inclusion Body Myopathy (HIBM) — all drugs for Hereditary Inclusion Body Myopathy (HIBM) →
• GNE Myopathy — all drugs for GNE Myopathy →

Sponsor

National Human Genome Research Institute (NHGRI)

Who can join

Adults 18 to 70, any sex, with Hereditary Inclusion Body Myopathy (HIBM) or GNE Myopathy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

\- Hereditary inclusion body myopathy (HIBM) is a genetic disorder caused by mutations in a gene called GNE. This gene is responsible for producing a sugar called sialic acid. Low levels of sialic acid may cause muscle problems. Symptoms of HIBM include walking difficulties and muscle weakness, which usually start in a person s 20s or 30s and become worse over time.

Researchers are studying a drug called ManNAc. It may be useful for treating HIBM. However, this drug is still being tested. Researchers want to see how ManNAc is absorbed into and removed from the blood. They will not be looking specifically at whether ManNAc can stop or slow the symptoms of HIBM.

Objectives:

* \<TAB\>To study how MaNAc is absorbed into and removed from the blood in people with HIBM.
* \<TAB\>To study of safety of ManNAc in people with HIBM.

Eligibility:

\- Individuals between 18 and 70 years of age who have HIBM.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
* Participants will have a 3 to 4-day inpatient stay for the main part of the study.
* Participants will be divided into groups of six. In each group, four will take ManNAc and two will take a placebo. Participants will not know which one they will receive.
* Participants will have a single dose of either ManNAc or placebo. They will be monitored for any possible side effects. Frequent blood samples will be collected during the 4-day stay.
* No treatment for HIBM will be provided as part of this study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. GNE myopathy: current update and future therapy.
   Nishino I, Carrillo-Carrasco N, Argov Z. · · 2015 · cited 121× · PMID 25002140 · DOI 10.1136/jnnp-2013-307051
2. Mutation update for GNE gene variants associated with GNE myopathy.
   Celeste FV, Vilboux T, Ciccone C, de Dios JK, et al · · 2014 · cited 95× · PMID 24796702 · DOI 10.1002/humu.22583
3. GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges.
   Carrillo N, Malicdan MC, Huizing M. · · 2018 · cited 69× · PMID 30338442 · DOI 10.1007/s13311-018-0671-y
4. CDG Therapies: From Bench to Bedside.
   Brasil S, Pascoal C, Francisco R, Marques-da-Silva D, et al · · 2018 · cited 66× · PMID 29702557 · DOI 10.3390/ijms19051304
5. Safety, pharmacokinetics and sialic acid production after oral administration of N-acetylmannosamine (ManNAc) to subjects with GNE myopathy.
   Xu X, Wang AQ, Latham LL, Celeste F, et al · · 2017 · cited 54× · PMID 28641925 · DOI 10.1016/j.ymgme.2017.04.010
6. Sialic acid deficiency is associated with oxidative stress leading to muscle atrophy and weakness in GNE myopathy.
   Cho A, Christine M, Malicdan V, Miyakawa M, et al · · 2017 · cited 48× · PMID 28505249 · DOI 10.1093/hmg/ddx192
7. Phenotypic stratification and genotype-phenotype correlation in a heterogeneous, international cohort of GNE myopathy patients: First report from the GNE myopathy Disease Monitoring Program, registry portion.
   Pogoryelova O, Cammish P, Mansbach H, Argov Z, et al · · 2018 · cited 46× · PMID 29305133 · DOI 10.1016/j.nmd.2017.11.001
8. Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a mouse model of GNE myopathy.
   Niethamer TK, Yardeni T, Leoyklang P, Ciccone C, et al · · 2012 · cited 45× · PMID 23122659 · DOI 10.1016/j.ymgme.2012.10.011