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

Sponsor

University of Cologne (Other)

Overall Status

Completed

CT.gov ID

NCT01281878

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Hyperoxaluria Type I	Drug: Vitamin B 6	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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