Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria

Stopped early · Not applicable

Conditions studied: Erythropoietic Protoporphyria (EPP), X Linked Erythropoietic Protoporphyria

In brief

In erythropoietic protoporphyria there is an accumulation of protoporphyrin IX (PPIX) in the plasma and liver. The reason it builds up is either the last step to make heme, insertion of iron into PPIX, is rate limiting or there is an increase in activity in the first step in the heme pathway. It may be possible to decrease the amount of PPIX made and see a decrease in symptoms. The first step to make heme is the key step in the pathway and it uses vitamin B6 as a cofactor. If the investigators can limit the amount of vitamin B6 the investigators can possibly reduce the activity of this rate limiting step. With decreased activity of the enzyme it may be possible for the body to utilize all the PPIX that is made so that none builds up.

Key facts

Study ID

NCT01550705

Run by

University of Utah

People needed

11

Starts

2012-03-01

Expected to finish

2015-12-01

Last updated by the study team

2017-01-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• All subjects will be enrolled in the Longitudinal Study of the Porphyrias.
• In patients with EPP the inclusion criteria are based on
• clinical features
• biochemical findings, as documented by laboratory reports of porphyria-specific testing performed after 1980
• molecular findings documenting the identification of a mutation in FECH or ALAS2 genes (molecular evidence of EPP is required for inclusion in the study).
• These data will be obtained from the Porphyria Rare Disease Clinical Research Consortium Longitudinal Study (RDCRN Protocol 7201). An individual must be willing to give written informed consent and be 18 years of age or greater.
• Autosomal EPP (EPP) and X-linked protoporphyria (XLEPP)
• Clinical features - a or b required
• A history of non-blistering cutaneous photosensitivity, usually with early age of onset.
• A diagnosis of EPP or XLEPP in a relative.
• Biochemical findings
• A marked increase in erythrocyte protoporphyrin [total erythrocyte protoporphyrin >200 ug/dL, or more than 1.5-fold increase relative to upper limit of normal of 80 ug/dL, with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLEPP). Note: Methods in some laboratories for measuring free erythrocyte protoporphyrin (FEP) actually measure zinc protoporphyrin, so these results cannot be relied upon for diagnosis or characterizing the phenotype in EPP and XLEPP.
• Increased plasma porphyrins with a fluorescence emission peak at \~634 nm.
• Normal urinary porphyrins (except in patients with hepatobiliary impairment), and normal ALA and porphobilinogen (PBG).
• Molecular findings - one of the following:
• A disease causing FECH mutation trans to the IVS3-48C>T low expression FECH allele (aEPP)
• Two disease-causing FECH mutations (EPP, recessive variant)
• A gain-of-function ALAS2 C-terminal deletion/exon 11 mutation (XLEPP)

You may not qualify if…

• Patients with a diagnosis of EPP that cannot be documented by DNA testing.
• Patients with evidence of active liver injury as defined by serum transaminase concentrations greater than three times the upper limit of normal, those with a history of recent (within 3 months of enrollment) or ongoing alcohol abuse, those with diabetes mellitus requiring therapy, renal insufficiency (serum creatinine >2.0 mg/ml) or evidence of malnutrition (based on subnormal plasma concentration of transthyretin) will be ineligible for participation in the study.
• Pregnant and/or lactating women will be excluded from the study.

Where it is running

• University of Utah School of Medicine — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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