Clinical Trial: The Clinical And Subclinical Effects on Arterial Stiffness of Bosentan in Patients With Systemic Sclerosis

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: The Clinical Efficacy And Subclinical Effects on Arterial STIFFNESS of Bosentan Therapy Added to Usual Care in Patients With Systemic Sclerosis With Digital Ulcers

Brief Summary: The aim of the study is to investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity (PWV) of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis (SSc) with digital ulcers (DU). Patients will be randomized into a group with usual care and bosentan (n=20) or usual care only (n=20). PWV will be assessed at baseline, 3 months and 12 months.

Detailed Summary:

Rationale: Digital ischemia is a major problem in patients with Raynaud's phenomenon (RP), especially in those with underlying connective tissue diseases such as systemic sclerosis (SSc). SSc is hallmarked by microvascular disease which can be assessed by nailfold capillary microscopy (NCM) to identify specific capillary patterns. However, it appears that vascular damage is not restricted to the capillaries, but may also extend to more upstream hand and forearm arteries. This may not only be reflected by clinically relevant structural abnormalities such as obliteration, but also by decreases in arterial function. The best characterised in RP is the occurrence of vasospasms after cold exposure. However, evidence points out that major stiffening of the arteries also occurs, potentially exaggerating digital ischemia and other vascular complications in SSc.

Objective: To investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis with digital ulcers.

Intervention:

Group 1: Usual care AND bosentan 62.5 mg twice daily, titrated to 125 mg twice daily after one month if tolerated (n=20) Group 2: Usual care only (n=20)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Bosentan is a registered product in the Netherlands. In this study, it will be used within its indication and not in combination with other products for which it has not been registered. Therefore no additional unknown uncertainties and increased overall risk are applicable for the investigational product. In the usual care group, treatment wi
Sponsor: University Medical Center Groningen

Current Primary Outcome: Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV) [ Time Frame: 3 months ]

assessed with Sphygmocor


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV) [ Time Frame: 12 months ]
    assessed with Sphygmocor
  • Right carotid-brachial arterial PWV (cbPWV) [ Time Frame: 3 and 12 months ]
    assessed with Sphygmocor
  • Left carotid-brachial arterial PWV (cbPWV) [ Time Frame: 3 and 12 months ]
    assessed with Sphygmocor
  • Right carotid-radial arterial PWV (crPWV) [ Time Frame: 3 and 12 months ]
    assessed with Sphygmocor
  • Left carotid-radial arterial PWV (crPWV) [ Time Frame: 3 and 12 months ]
    assessed with Sphygmocor
  • Local PWV of the right radial artery (rPWV) [ Time Frame: 3 and 12 months ]
    ultrasound assessment using a MyLabOne Vascular machine
  • Local PWV of the left radial artery (rPWV) [ Time Frame: 3 and 12 months ]
    an ultrasound assessment using a MyLabOne Vascular machine
  • Local PWV of the right brachial artery (bPWV) [ Time Frame: 3 and 12 months ]
    an ultrasound assessment using a MyLabOne Vascular machine
  • Local PWV of the left brachial artery (bPWV) [ Time Frame: 3 and 12 months ]
    an ultrasound assessment using a MyLabOne Vascular machine
  • Microangiopathy Evolution Score (MES) [ Time Frame: 3 and 12 months ]
    With nailfold capillary microscopy
  • Capillaroscopic Skin Ulcer Risk Index (CSURI) [ Time Frame: 3 and 12 months ]
    With nailfold capillary microscopy
  • Prognostic Index for Digital Lesions (PILD) [ Time Frame: 3 and 12 months ]
    With nailfold capillary microscopy
  • Mean widened capillaries of 8 fingers (dig 2-5) [ Time Frame: 3 and 12 months ]
    number per finger, assessed with nailfold capillary microscopy
  • Mean giant capillaries of 8 fingers (dig 2-5) [ Time Frame: 3 and 12 months ]
    number per finger, assessed with nailfold capillary microscopy
  • Mean capillary density of 8 fingers (dig 2-5) [ Time Frame: 3 and 12 months ]
    number per mm per finger, assessed with nailfold capillary microscopy
  • Mean loop width of 8 fingers (dig 2-5) [ Time Frame: 3 and 12 months ]
    mm per capillary per finger, assessed with nailfold capillary microscopy
  • Blood flow in the hands in region of interest (ROI) 1: distal of the proximal interphalangeal (PIP) joint of the 3 middle fingers [ Time Frame: 3 and 12 months ]
    Measured by Laser Doppler Perfusion Imaging
  • Blood flow in the hands in ROI 2: distal of the metacarpal joints and proximal of the PIP joint [ Time Frame: 3 and 12 months ]
    Measured by Laser Doppler Perfusion Imaging
  • Blood flow in the hands in ROI 3: the hand proximal of the metacarpal joints [ Time Frame: 3 and 12 months ]
    Measured by Laser Doppler Perfusion Imaging
  • Skin Autofluorescence [ Time Frame: 3 and 12 months ]
    assessed with the AGE Reader
  • Number of new digital ulcers [ Time Frame: 3 and 12 months ]
    Number
  • Time to healing of digital ulcers [ Time Frame: 3 and 12 months ]
    In days
  • Urine albumin/creatinine ratio (ACR) [ Time Frame: 3 and 12 months ]
    Measured in two separate morning samples of urine
  • Plasma N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) [ Time Frame: 3 and 12 months ]
    assessed using a routine assay
  • Serum levels of matrix metalloproteinase 3 [ Time Frame: 3 and 12 months ]
    measured according to the manufacturer's instructions
  • Serum levels of matrix metalloproteinases 9 [ Time Frame: 3 and 12 months ]
    determined using in-house enzyme-linked immunosorbent ass

    Original Secondary Outcome: Same as current

    Information By: University Medical Center Groningen

    Dates:
    Date Received: June 15, 2015
    Date Started: June 2015
    Date Completion: June 2017
    Last Updated: June 19, 2015
    Last Verified: June 2015