Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01550705
• Date of registration: 05/03/2012
• Prospective Registration: No
• Primary sponsor: University of Utah
• Public title: Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria INHEPP
• Scientific title: Quantification of the Effects of Isoniazid Treatment on Erythrocyte and Plasma Protoporphyrin IX Concentration and Plasma Aminolevulinic Acid in Patients With Erythropoietic Protoporphyria
• Date of first enrolment: March 2012
• Target sample size: 11
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01550705
• Study type: Interventional
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: John D Phillips, PhD
• Affiliation: University of Utah

Key inclusion & exclusion criteria

Inclusion Criteria:

- All subjects will be enrolled in the Longitudinal Study of the Porphyrias.

- In patients with EPP the inclusion criteria are based on

1. clinical features

2. biochemical findings, as documented by laboratory reports of porphyria-specific
testing performed after 1980

3. 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)

Exclusion Criteria:

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

X Linked Erythropoietic Protoporphyria

Erythropoietic Protoporphyria (EPP)

Intervention(s)

Drug: Isoniazid

Primary Outcome(s)

Change in Plasma Protoporphyrin IX Level [Time Frame: Baseline and 3 Months]

Secondary Outcome(s)

Participants With Increased Sun Sensitivity [Time Frame: Baseline and 3 Months]

Secondary ID(s)

U54DK083909

UTINH

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Icahn School of Medicine at Mount Sinai

University of Alabama at Birmingham

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

University of California, San Francisco

University of Texas

Results

• Results available: Yes
• Date Posted: 16/01/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01550705