Trial on Treatment of Patients With Primary Hyperoxaluria Type I With Pyridoxal-phosphate (PHOX-B6-Pilot)

PILOTSTUDIE ZUR PYRIDOXALPHOSPHATTHERAPIE BEI PATIENTEN MIT PRIMÄRER HYPEROXALURIE TYP I (PHOX-B6-PILOT) Pilot Trial on Treatment of Patients With Primary Hyperoxaluria Type I With Pyridoxal-phosphate

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.

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria Type I
• Intervention / Treatment: Drug: Vitamin B 6

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50931
      • Children´s Hospital University of Cologne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyridoxal-phosphate; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Cologne

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 20, 2011
• First Submitted That Met QC Criteria: January 21, 2011
• First Posted (Estimate): January 24, 2011

Study Record Updates

• Last Update Posted (Estimate): October 29, 2012
• Last Update Submitted That Met QC Criteria: October 26, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: primary hyperoxaluria; Pyridoxal-phosphate
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Vitamin B 6; Pyridoxal; Pyridoxine
• Other Study ID Numbers: Uni-Koeln-1251