Simvastatin Treatment of Pachyonychia Congenita

NCT01382511 | Unknown

• 1 other identifier: 0462-09-TLV
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Simvastatin and related statins, such as compactin, are able to inhibit the constitutive expression of inducible/repressible keratin genes such as K6a and K17. This effect is due to the reported ability of statins to inhibit STAT1 expression (Lee et al., 2007). The constitutive K6a promoter activity is dependent on STAT1 and blocked by simvastatin or siRNA against STAT1. This STAT1-dependent constitutive expression of K6a, is independent of JAK (Janus family of kinases). Thus simvastatin is capable of down-regulating both the constitutive and interferon-inducible expression of PC-related keratins such as K6a and K17. Therefore, this class of molecule has potential for the treatment of PC or related inherited disorders where the causative mutation resides in an inducible/repressible keratin gene such as K6a or K17. Simvastatin or other statins approved for human use might be delivered either orally, as is currently the case for cholesterol-lowering treatment or, if higher therapeutic doses are required in skin for reduction of hyperkeratosis in PC or in related keratinizing disorders, this might be achieved by topical formulations.

Conditions

Pachyonychia Congenita

Outcome Measures

Primary Outcomes (1)

• Assessment of decreased hyperkeratosis

  Decreased hyperkeratosis

  six months

Interventions

Simvastatine DRUG

80 mg

Eligibility Criteria

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

You may qualify if:

• Patients with pachyonychia congenita with known mutations in keratin 6a. -

You may not qualify if:

• The use of concomitant medications known to interact with simvastatin.
• This would include itraconazole, ketoconazole, fluconazole, gemfibrozil, verapamil, diltiazem, mibefradil, erythromycin, clarithromycin, telithromycin, cyclosporine, ritonavir, nefazodone, danazol, amiodarone, Rifampin, and carbamazepine.
• During the study subjects must agree to avoid grapefruit juice.
• Also excluded are patients with a past history of myopathy, or impaired liver function.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

MeSH Terms

Conditions

Pachyonychia Congenita

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Nail Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 27, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2014
• Last Updated: June 27, 2011

Record last verified: 2009-10