Simvastatin Treatment of Pachyonychia Congenita

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2009 by Tel-Aviv Sourasky Medical Center.
Recruitment status was  Not yet recruiting
Information provided by:
Tel-Aviv Sourasky Medical Center Identifier:
First received: June 14, 2011
Last updated: June 23, 2011
Last verified: October 2009

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.

Condition Intervention
Pachyonychia Congenita
Drug: Simvastatine

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Simvastatin Treatment of Pachyonychia Congenita

Resource links provided by NLM:

Further study details as provided by Tel-Aviv Sourasky Medical Center:

Primary Outcome Measures:
  • Assessment of decreased hyperkeratosis [ Time Frame: six months ] [ Designated as safety issue: Yes ]
    Decreased hyperkeratosis

Estimated Enrollment: 10
Study Start Date: July 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Simvastatine
    80 mg

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
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  More Information

Responsible Party: Department of Dermatology, Tel Aviv Sourasky Medical Center Identifier: NCT01382511     History of Changes
Other Study ID Numbers: 0462-09-TLV 
Study First Received: June 14, 2011
Last Updated: June 23, 2011
Health Authority: Israel: The State of Israel Ministre of health

Additional relevant MeSH terms:
Pachyonychia Congenita
Congenital Abnormalities
Ectodermal Dysplasia
Genetic Diseases, Inborn
Nail Diseases
Skin Abnormalities
Skin Diseases
Skin Diseases, Genetic processed this record on May 23, 2016