(layman's term not used by patient groups not applicable) Porphyria
Conditions
Interventions
None listed
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: (see Protocol C1. page 14, paragraph 4.2 Inclusion criteria) Acute porphyria patients: - Age 12 years and older - Decreased enzyme activity of porphobilinogen deaminase (acute intermittent porphyria), protoporphyrinogen oxidase (variegate porphyria), and coproporphyrinogen oxidase (hereditary coproporphyria), or an inactivating mutation in the relevant gene or both. - Symptomatic and asymptomatic patients with an identified acute porphyria mutation or biochemical proof of an acute porphyric attack/episode;Healthy controls are unaffected sibs, spouses or friends selected via the cases.;For both groups a signed informed consent form is required.
Exclusion criteria
Exclusion criteria: (see Protocol C1. page 14) Subjects with an increased risk of complication will be excluded from liver biopsy according to guidelines of the American Association for the Study of Liver Diseases, and other risk factors based on local experience.;Contraindications for fine needle biopsy with a 20G needle:;-Under 18 years of age -Uncooperative patient -Unable to give informed consent -Severe coagulopathy -Infection of the hepatic bed -Extra hepatic biliary obstruction -Ascites -Morbid Obesity -Possible vascular lesions -Amyloidosis -Hydatid disease -Liver fibrosis/ cirrhosis -Pre-existent malignancy in the liver -Any bleeding disorder, including those on aspirin and NSAIDS or any other anticoagulant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (also see: C1. Protocol, page 19, paragraph 8.1.1) Retrospective family cohort study: Complete family tree obtainment. Pedigree information including date of birth, date of death and cause of death of family members, will be collected through patient interview (either during clinic visits or by mail or phone). Patient information will be cross-referenced with Dutch genealogy databases to ensure accuracy. Data will be used for estimation of a standardized mortality ratio and other statistics of the Dutch porphyria cohort. Prospective genotype-fenotype variation case-control study: - Acute porphyric attacks (Definition of acute attack is : abdominal pain with a steep increase in delta-aminolevulinic acid levels (plasma or urine), with a pain duration of >= 1 day.) - Renal function / incidence of renal insufficiency - Blood pressure / incidence of hypertension - Incidence and prevalence of hepatocellular carcinoma | — |
Secondary
| Measure | Time frame |
|---|---|
| (also see: Protocol C1, page 19/20, paragraph 8.1.2 - 8.1.3) Secondary study parameters/endpoints - Blood pressure - Renal function (Creatinine and GFR) - Plasma/urine porphyrin and precursor levels - Pregnancy complications - Previous attacks with pain measures based on VAS scales (0-10); past and present physical complaints: abdominal pain, paresis, psychosis, epilepsy - DNA methylation PBGd gene in blood samples and hepatocytes - Heart rate variability assessment, with EKG for 1 hour - Enzyme activity in hepatocytes - Hair cortisol - Specific enzyme activity and specific mRNA levels in erythrocytes, fibroblasts and / or hepatocytes - Liver function - Liver fibrosis/ cirrhosis - Incidence and prevalence of hepatocellular carcinoma Other study parameters - QOL questionnaire scores: SF36, DS14, HADS, Open qualitative questionnaire directed at burden by acute porphyria - Perceived Stress Scale (PSS) (to correlate perceived stress with hair cortisol levels) | — |
Countries
Netherlands
Outcome results
None listed