Clinical trial NCT01281878: Trial on Treatment of Patients With Primary Hyperoxaluria Type I With Pyridoxal-phosphate
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Hyperoxaluria Type I
Keywords: primary hyperoxaluria
Pyridoxal-phosphate
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2011-01-24
Enrollment: 12
Sex: ALL
Minimum age (years): 5
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 6 month
Secondary outcomes:
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Children´s Hospital University of Cologne
state: NRW
Study officials:
References:
citation: 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.