Simvastatin Treatment of Pachyonychia Congenita

Pachyonychia Congenita Clinical Trial

Official title:

Simvastatin Treatment of Pachyonychia Congenita

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01382511
• Other study ID #: 0462-09-TLV
• Status: Not yet recruiting
• Phase: N/A
• First received: June 14, 2011
• Last updated: June 23, 2011
• Start date: July 2011

Study information

• Verified date: October 2009
• Source: Tel-Aviv Sourasky Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: The State of Israel Ministre of health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pachyonychia Congenita

Intervention

Drug:
• Simvastatine
80 mg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of decreased hyperkeratosis	Decreased hyperkeratosis	six months	Yes