Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis
Raktažodžiai
Santrauka
apibūdinimas
Nephrogenic systemic fibrosis (NSF) is a recently described, extremely debilitating and painful condition that affects individuals with renal failure. Recent reports suggest an association between gadolinium exposure during magnetic resonance (MR) studies and the subsequent development of NSF in patients with chronic renal failure. NSF is characterized by rapidly progressive skin hardening, tethering and hyperpigmentation, predominantly on the extremities. Visceral involvement is rare. Skin biopsies of early NSF lesions demonstrate thickened collagen bundles, mucin deposition, angiogenesis and numerous dermal spindle cells that stain with antibodies to cluster of differentiation 34 (CD34) and procollagen. Cutaneous changes of NSF are present in up to 13% of individuals receiving hemodialysis. Among those patients with clinical evidence of NSF, the principle investigator of this protocol has recently reported that NSF is associated with increased early mortality at 24-months.
There is no proven therapy for this devastating disorder. Anecdotal reports have shown modest improvement in joint mobility and decreased skin thickening with extracorporeal photopheresis and pentoxyphylline.
Increased transforming growth factor (TGF)-beta1 messenger ribonucleic acid (mRNA) on immunostaining has been observed in skin, fascia and striated muscle. Imatinib mesylate, a tyrosine kinase inhibitor, prevents TGF-beta-induced stimulation of collagen and extracellular matrix protein synthesis as well as mRNA expression by normal fibroblasts. This observation led the principal investigator to evaluate imatinib mesylate 400 milligrams (mg) orally (p.o.) daily for 1 year in two participants with NSF. The result was significant softening of previously hardened skin with increased mobility of skin that previously had been tethered to the underlying fascia. After one month of imatinib mesylate, one of the two participants had a 20 degree reduction of his knee flexion contractures.
Datos
| Paskutinį kartą patikrinta: | 03/31/2017 |
| Pirmasis pateikimas: | 05/07/2008 |
| Numatytas registravimas pateiktas: | 05/11/2008 |
| Pirmas paskelbtas: | 05/12/2008 |
| Paskutinis atnaujinimas pateiktas: | 04/09/2017 |
| Paskutinis atnaujinimas paskelbtas: | 05/18/2017 |
| Pirmųjų rezultatų pateikimo data: | 04/09/2017 |
| Pirmojo QC rezultatų pateikimo data: | 04/09/2017 |
| Pirmųjų paskelbtų rezultatų data: | 05/18/2017 |
| Faktinė studijų pradžios data: | 11/30/2007 |
| Numatoma pirminio užbaigimo data: | 06/30/2009 |
| Numatoma studijų užbaigimo data: | 06/30/2009 |
Būklė ar liga
Intervencija / gydymas
Drug: Imatinib Mesylate (IM) Treatment
Fazė
Rankų grupės
| Ranka | Intervencija / gydymas |
|---|---|
| Experimental: Imatinib Mesylate (IM) Treatment Imatinib mesylate 400 milligrams (mg) orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia. | Drug: Imatinib Mesylate (IM) Treatment 400 mg p.o. daily for 4 months. Dosage was reduced to 200 mg if participants develop gastrointestinal intolerance or alopecia. |
Tinkamumo kriterijai
| Amžius, tinkami studijuoti | 18 Years Į 18 Years |
| Tinkamos studijoms lytys | All |
| Priima sveikus savanorius | Taip |
| Kriterijai | Inclusion Criteria: - Age > 18 years - Biopsy-proven NSF - Ability to give consent Exclusion Criteria: - Known sensitivity to imatinib mesylate or to any of its components - Pregnant or lactating woman - Bullous dermatologic disease - Aspartate aminotransferase / alanine aminotransferase (AST/ALT) >3 x upper limit of normal - Severe congestive heart failure [New York Heart Association (NYHA) Class III or IV] - Patients who have received Gleevec in the past 12 months |
Rezultatas
Pirminės rezultatų priemonės
1. Percentage Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Assess Skin Tethering [Baseline and Month 4]
Antrinės rezultatų priemonės
1. Change From Baseline in Maximal Extension of Elbows and Knees [Baseline and Month 4]
2. Change From Baseline in Histologic Appearance of Skin Biopsy [Baseline and Month 4]
3. Change From Baseline in Visual Analog Scale (VAS) for Pain [Baseline and Month 4]
4. Change From Baseline in Health Assessment Questionnaire (HAQ) Score [Baseline and Month 4]
5. Change From Baseline in Short Form 36 (SF-36) Score [Baseline and Month 4]
