Simvastatin Treatment of Pachyonychia Congenita

Not Applicable

• Conditions: Pachyonychia Congenita

• Registration Number: NCT01382511
• Lead Sponsor: Tel-Aviv Sourasky Medical Center

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2009-10
• Study First Submitted: 2011-06-14
• Study First Submitted QC: 2011-06-23
• Last Update Submitted: 2011-06-23
• Study First Posted: 2011-06-27
• Last Update Posted: 2011-06-27
• Study Start: 2011-07
• Primary Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

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

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Assessment of decreased hyperkeratosis	six months	Decreased hyperkeratosis