Simvastatin Treatment of Pachyonychia Congenita

NCT ID: NCT01382511

Last Updated: 2011-06-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Simvastatine

80 mg

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Tel Aviv Sourasky Medical Center

Other Identifiers

0462-09-TLV

Identifier Type: -

Identifier Source: org_study_id