Prognostic Influence of Light Rheography Measurement of Patients With Secondary Raynaud Syndrome With Ulcers on Hands (Anti-Vasospasm)

Monocenter, IIT, Open Controlled and Prospectiv Study to Define the Prognostic Influence of Light Rheography Measurement of Patients With Secundary Raynaud Syndrome With Ulcers at Fingertips Throughout the Medicinal Therapy

The purpose of this study is to evaluate the prognostic influence of light rheography measurement at the fingertips from subjects with secundary Raynaud syndrome.

Study Overview

• Status: Unknown
• Conditions: Raynaud's Phenomenon; Skin Necrosis
• Intervention / Treatment: Drug: Prostavasin; Drug: Tracleer

Detailed Description

Digital Ulcers (DU) belong to one of the most prevalent complications of systemic scleroses, leading in course to considerable impairment in everyday and professional life. The aetiology of the emergence of DU in patients with systemic scleroses (SSc) is complex, whereas the disease itself is primarily characterized by a vasculopathy of the small arterial vessels. In the course of the disease this chronic infection leads to fibrotic intimal hyperplasia, adventitial fibrosis, and thus to a significant lumen narrowing. So far, a number of independent risk factors have been identified, such as male gender, chronic infections of the esophagus, pulmonary-arterial hypertension, evidence of specific antibodies (e.g. anti-Scl70) in the blood, or the a previous manifestation of a Raynoud Syndrom.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christoph Hehrlein, Prof. Dr. med.; Phone Number: +49 761 270 77090; Email: christoph.hehrlein@uniklinik-freiburg.de
• Study Contact Backup: Name: Mark Kerber, Dr. med.; Phone Number: +49 761 270 36920; Email: mark.kerber@uniklinik-freiburg.de

Study Locations

• Germany
  • Baden Württemberg
    • Freiburg, Baden Württemberg, Germany, 79106
      • Recruiting
      • University Freiburg
      • Contact: Mark Kerber, MD; Email: mark.kerber@uniklinik-freiburg.de
      • Contact: christoph Hehrlein, MD; Email: christoph.hehrlein@uniklinik-freiburg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with Limited or diffuse systemic sclerosis/scleroderma with at least one ulcera at fingertip
• Age > 18 Years
• Weight > 40 Kg

Exclusion Criteria:

• Sympathectomy
• Ulcers due to other condition (PVD, DM, Thromboangiitis obliterans etc.)
• Antibiotic concomitant medication
• Therapy with Prostanoids within the last 4 weeks
• Previous Bosentan therapy
• Severe liver and renal insufficiency(creatinin >2.0 mg/dl;AST/ALT > 3X UNL)
• severe cardiac- pulmonal diseases
• Untreated or therapy refractory Hypertension
• Noncompliance
• Pregnancy or nursing (Pregnancy test required)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Prostavasin	Drug: Prostavasin; Prostavasin 60 µg i.v, 5 days per week for 2 weeks; Other Names: Aprostadil
Active Comparator: Prostavasin + Bosentan	Drug: Prostavasin; Prostavasin 60 µg i.v, 5 days per week for 2 weeks; Other Names: Aprostadil; Drug: Tracleer; 14 days 62,5 mg Bosentan p.o 140 days 125 mg Bosentan p.o; Other Names: Bosentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of the blood flow before, during and after the medical therapy	The primary objective of this study is defined by the dynamics of the (post)capillary blood flow before (baseline value) and 12 weeks after treatment, measured by means of the LRR. In doing so, the therapeutic effect, in terms of the change in (post)capillary blood flow after treatment compared to baseline value, is to be quantitatively determined.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emerge of new ulcers	Additionally, it is to be examined if new DUs emerge after 24 weeks or not. The prospects for recovery of the DU will be investigated by means of visual analogue scale (VAS), photo-documentation, and D-LRR after 2, 6, 12, and 24 weeks of medicinal therapy. Furthermore, as mentioned above, the change in the HIF-1alpha gene expression before (baseline value) and 6 weeks after treatment is to be analyzed.	> 24 weeks

Collaborators and Investigators

• Sponsor: Christoph Hehrlein
• Collaborators: Actelion
• Investigators: Principal Investigator: Mark Kerber, Dr. med., Universitätsklinik Freiburg

Publications and helpful links

General Publications

• -Distler O, Gay S. [Scleroderma]. Internist (Berl) 2010; 51(1):30-38. -Mouthon L, Mestre-Stanislas C, Berezne A et al. Impact of digital ulcers on disability and health-related quality of life in systemic sclerosis. Ann Rheum Dis 2010; 69(1):214-217. -Denton C, Krieg T, Guillevin L. The burden of complications in patients with digital ulcers (DU) and systemic sclerosis (SSc): Preliminary findings from the DUO-Registry. 2009: 273. -Korn JH, Mayes M, Matucci CM et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004; 50(12):3985-3993. -Block JA, Sequeira W. Raynaud's phenomenon. Lancet 2001; 357(9273):2042-2048.
• -Sunderkotter C, Herrgott I, Bruckner C et al. Comparison of patients with and without digital ulcers in systemic sclerosis: detection of possible risk factors. Br J Dermatol 2009; 160(4):835-843. -Muller-Ladner U. Akrale Ischämiesyndrome: vom Raynaud-Syndrom zur systemischen Sklerose. Bremen/London/Boston: UNI-MED Verlag AG, 2009 -Arab A, Kuemmerer K, Wang J et al. Oxygenated perfluorochemicals improve cell survival during reoxygenation by pacifying mitochondrial activity. J Pharmacol Exp Ther 2008; 325(2):417-424. -Pope J, Fenlon D, Thompson A et al. Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2000;(2):CD000953. -Kawald A, Burmester GR, Huscher D et al. Low versus high-dose iloprost therapy over 21 days in patients with secondary Raynaud's phenomenon and systemic sclerosis: a randomized, open, single-center study. J Rheumatol 2008; 35(9):1830-1837. -Kowal-Bielecka O, Landewe R, Avouac J et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 2009; 68(5):620-628. -Sunderkotter C, Riemekasten G. [Raynaud phenomenon in dermatology:Part 2:therapy]. Hautarzt 2006; 57(10):927-938. -Ludwig M. Angiologie in Klinik und Praxis. 1 ed. Stuttgart: Thieme Verlag, 1998; 1-334.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 22, 2011

Study Record Updates

• Last Update Posted (Estimate): December 15, 2014
• Last Update Submitted That Met QC Criteria: December 12, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Raynaud's phenomenon; Morbus Raynaud; Ulcera Hands, Toes; Vasospastic disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Peripheral Vascular Diseases; Necrosis; Raynaud Disease; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Urological Agents; Platelet Aggregation Inhibitors; Endothelin Receptor Antagonists; Bosentan; Alprostadil
• Other Study ID Numbers: 2011-002127-17