Triheptanoin Treatment Trial for Patients With Adult Polyglucosan Body Disease

NCT ID: NCT00947960

Last Updated: 2018-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2015-07-31

Brief Summary

The purpose of the study is to determine if triheptanoin is an effective treatment for the symptoms of Adult Polyglucosan Body Disease.

Detailed Description

Adult polyglucosan disease is a progressive neurogenetic disorder characterized by neurogenic bladder, progressive difficulty with walking, and sensory abnormalities in the lower extremities which typically present in the 4th or 5th decade of life. The pathogenesis of the disease includes the accumulation of intracellular polyglucosan bodies (amylopectin-like polysaccharides) in the peripheral nerves as well as the central nervous system cells and is often associated with brancher enzyme deficiency which causes improper glycogen formation. It is hypothesized that decreased glycogen degradation leads to energy deficit in the nervous system cells. Therefore, anaplerotic therapy may supply needed substrate to the citric acid cycle to correct the energy deficit. This intervention may slow, halt or reverse the progression of the disease, for which there is no effective treatment. The trial involves 18 subjects ingesting a diet supplemented with triheptanoin, a 7 carbon triglyceride or a placebo of vegetable oil at a dose of 1-2 g/kg/24 hours in a randomized crossover controlled double blind study. The study lasts one year with patients receiving triheptanoin for 6 mo and the placebo oil for 6 mo. Safety monitoring includes urine organic acids and acyl carnitine profile.

Conditions

Adult Polyglucosan Body Disease; Glycogen Brancher Enzyme Deficiency; Glycogen Storage Disease Type IV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active/Placebo

Subjects receive 1-2 grams/kilogram body weight triheptanoin divided into 4 equal doses taken with meals and snack for 6 months crossing over to receive placebo vegetable oil at the same dose and frequency for the next 6 months during the randomization phase.

Group Type: OTHER

Triheptanoin

Intervention Type: DRUG

1-2 grams triheptanoin (drug)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months.

Vegetable Oil

Intervention Type: OTHER

1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 g triheptanoin (drug)/kilogram body weight for 6 months.

Placebo/Active

Subjects receive 1-2 grams/kilogram body weight placebo vegetable oil divided into 4 equal doses taken with meals and snack for 6 months crossing over to receive triheptanoin at the same dose and frequency for the next 6 months during the randomization phase.

Group Type: OTHER

Triheptanoin

Intervention Type: DRUG

1-2 grams triheptanoin (drug)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months.

Vegetable Oil

Intervention Type: OTHER

1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 g triheptanoin (drug)/kilogram body weight for 6 months.

Interventions

Triheptanoin

1-2 grams triheptanoin (drug)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months.

Intervention Type: DRUG

Vegetable Oil

1-2 grams vegetable oil (placebo)/kilogram body weight divided into 4 equal doses per day taken with meals and a snack for 6 months followed by 1-2 g triheptanoin (drug)/kilogram body weight for 6 months.

Intervention Type: OTHER

Other Intervention Names

Placebo

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of APBD by the presence of mutations of the GBE1 gene in both alleles or brancher enzyme deficiency
• Willing and able to travel to Dallas TX
• Able to tolerate dietary oil
• Able to provide informed consent

Exclusion Criteria

• Intercurrent medical conditions that would confound the assessment of efficacy, such as HIV or diabetes
• Patients who are wheelchair bound
• Patients deemed unsuitable for the study by the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: collaborator

Baylor Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raphael Schiffmann, M.D, M.H.Sc

Role: PRINCIPAL_INVESTIGATOR

Institute of Metabolic Disease

Locations

Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Countries

France

References

Schiffmann R, Wallace ME, Rinaldi D, Ledoux I, Luton MP, Coleman S, Akman HO, Martin K, Hogrel JY, Blankenship D, Turner J, Mochel F. A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome. J Inherit Metab Dis. 2018 Sep;41(5):877-883. doi: 10.1007/s10545-017-0103-x. Epub 2017 Nov 6.

Reference Type: DERIVED

PMID: 29110179 (View on PubMed)

Other Identifiers

009-103

Identifier Type: -

Identifier Source: org_study_id