Trial on Treatment of Patients With Primary Hyperoxaluria Type I With Pyridoxal-phosphate

NCT01281878 | Completed Phase 2

• 1 other identifier: Uni-Koeln-1251
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators will prospectively analyze the reduction of urinary oxalate excretion under the treatment with PLP in dosages of 5mg/kg/day up to 20 mg/kg/day and serum level response relationship with PLP as an i.v. solution used orally in 12 patients with primary hyperoxaluria type I as an inherited autosomal-recessive-disorder leading to increased endogenous oxalate production, urolithiasis and end stage renal disease.

Conditions

Primary Hyperoxaluria Type I

Keywords

primary hyperoxaluria; Pyridoxal-phosphate

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the study is the reduction of the urinary oxalate excretion (percentage change in urinary oxalate, expressed as mmol/1.73 m2 /day) at week 24 compared to baseline.

  6 month

Study Arms (1)

Pyridoxal-phosphate

EXPERIMENTAL

Treatment with pyridoxal-phosphate in increasing dosages every six weeks starting with 5mg/kg body weight up to 20 mg/kg body weight. treatment duration 24 weeks

Drug: Vitamin B 6

Interventions

Vitamin B 6 DRUG

Oral solution of pyridoxal phosphate start with 5mg per kg body weight per day in two dosages over 6 weeks, increase stepwise by 5mg/kg body weight every 6 weeks up to 20 mg/kg body weight/d.

Pyridoxal-phosphate

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Documentation of diagnosis of PH I by any one of the following:
• Liver biopsy confirmation of deficient liver specific peroxisomal alanine-glyoxylate aminotransferase, (AGT or mislocalization of AGT from peroxisomes to mitochondria)
• Homozygosity or compound heterozygosity for a known mutation in the causative gene (AGXT) for PH I
• Male or female subjects between 5 years and 60 years of age
• Renal function defined as an estimated GFR \> 60 ml/min normalized to 1.73 m2 body surface area
• Subjects receiving pyridoxal-phosphate before the study must be willing to discontinue therapy with pyridoxal-phosphate for a wash out phase of at least 4 weeks but always until normalization of serum pyridoxal-phosphate levels
• Written informed consent from patients and/or legally acceptable representatives

You may not qualify if:

• Pregnant or lactating women
• Women of child-bearing potential who are not using a highly effective contraception method with a pearl-index \< 1. Highly effective contraception methods are oral, transdermal, injectable, or implanted contraceptives, IUD, abstinence, or sterile sexual partner and must agree to continue using such precautions during the pyridoxal-phosphate study
• Subjects post liver or kidney transplantation or combined transplantation
• Chronic diarrhoea with the risk of malabsorption
• Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator, is indicative of a disease that would compromise the safety taking pyridoxal-phosphate per os and the absorption
• Subjects participating in other clinical trials with investigational products 4 weeks prior to trial entry, during the trial and 4 weeks after the trial
• Subjects who are unable to take the trial medication
• Subjects who are unable to collect 24-hour urine samples or follow other study procedures
• Subjects who are under treatment with L-Dopa, Isoniazid, D-Penicillamine (interactions between these drugs and pyridoxal-phosphate are known and might influence serum pyridoxal-phosphate levels)
• Subjects with known allergies to substances of contents (e.g. Potassium sorbet, raspberry syrup)
• Subjects confined to an institution on judicial or official behalf
• Subjects who are in dependency to the sponsor or the PI of the trial

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (1)

Children´s Hospital University of Cologne

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Related Publications (1)

• Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. doi: 10.2215/CJN.06820613. Epub 2014 Jan 2.

  PMID: 24385516 DERIVED

MeSH Terms

Conditions

Hyperoxaluria; Hyperoxaluria, Primary

Interventions

Vitamin B 6

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Bernd Hoppe

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 24, 2011
• Study Start: December 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 29, 2012

Record last verified: 2012-10

Locations

DE (1)