Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria

NCT01550705 | Terminated Results DMC

• 2 other identifiers: UTINHU54DK083909
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Erythropoietic Protoporphyria (EPP); X Linked Erythropoietic Protoporphyria

Keywords

Protoporphyria; Porphyria; Porphyrins

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Protoporphyrin IX Level

  Plasma Protoporphyrin IX will be measured at baseline and at 3 months

  Baseline and 3 Months

Secondary Outcomes (1)

• Participants With Increased Sun Sensitivity

  Baseline and 3 Months

Study Arms (1)

Isoniazid

EXPERIMENTAL

Subjects will receive isoniazid daily for 2 months. Subjects will be seen every 2 weeks to obtain lab samples and health check.

Drug: Isoniazid

Interventions

Isoniazid DRUG

Isoniazid 5 mg/Kg up to 300 mg per day. Oral tablets. 2 months.

Isoniazid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects will be enrolled in the Longitudinal Study of the Porphyrias.
• clinical features
• biochemical findings, as documented by laboratory reports of porphyria-specific testing performed after 1980
• 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)

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.

Sponsors & Collaborators

• University of Utah: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Alabama at Birmingham: collaborator
• University of California, San Francisco: collaborator
• University of Texas: collaborator

Study Sites (1)

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Related Links

• American Porphyria Foundation

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Porphyrias

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: John D. Phillips, Ph.D.
• Organization: University of Utah

john.phillips@hsc.utah.edu

801-581-6650

Study Officials

• John D Phillips, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: March 5, 2012
• First Posted: March 12, 2012
• Study Start: March 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 16, 2017
• Results First Posted: January 16, 2017

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)