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Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria (INHEPP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01550705
Recruitment Status : Terminated (Interim analysis demonstrated the treatment was not effective)
First Posted : March 12, 2012
Results First Posted : January 16, 2017
Last Update Posted : January 16, 2017
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Icahn School of Medicine at Mount Sinai
University of Alabama at Birmingham
University of California, San Francisco
University of Texas
Information provided by (Responsible Party):
John Phillips, University of Utah

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Erythropoietic Protoporphyria (EPP) X Linked Erythropoietic Protoporphyria Drug: Isoniazid Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Quantification of the Effects of Isoniazid Treatment on Erythrocyte and Plasma Protoporphyrin IX Concentration and Plasma Aminolevulinic Acid in Patients With Erythropoietic Protoporphyria
Study Start Date : March 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Isoniazid
Subjects will receive isoniazid daily for 2 months. Subjects will be seen every 2 weeks to obtain lab samples and health check.
Drug: Isoniazid
Isoniazid 5 mg/Kg up to 300 mg per day. Oral tablets. 2 months.

Primary Outcome Measures :
  1. Change in Plasma Protoporphyrin IX Level [ Time Frame: Baseline and 3 Months ]
    Plasma Protoporphyrin IX will be measured at baseline and at 3 months

Secondary Outcome Measures :
  1. Participants With Increased Sun Sensitivity [ Time Frame: Baseline and 3 Months ]
    Study participants were asked to report after 3 months if they had experienced an increase in subjective measures of sun sensitivity during the trial. Reported outcome is the number of study participants who reported increased sun sensitivity

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01550705

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United States, Utah
University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Icahn School of Medicine at Mount Sinai
University of Alabama at Birmingham
University of California, San Francisco
University of Texas
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Principal Investigator: John D Phillips, PhD University of Utah
Additional Information:
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Responsible Party: John Phillips, Principle Investigator, University of Utah Identifier: NCT01550705    
Other Study ID Numbers: UTINH
U54DK083909 ( U.S. NIH Grant/Contract )
First Posted: March 12, 2012    Key Record Dates
Results First Posted: January 16, 2017
Last Update Posted: January 16, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by John Phillips, University of Utah:
Additional relevant MeSH terms:
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Protoporphyria, Erythropoietic
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Metabolic Diseases
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents