The purpose of this study is to assess feasibility, safety and preliminary efficacy of Extracorporeal Photopheresis in the treatment of active diffuse cutaneous systemic sclerosis (dcSSc). This pilot study will help to determine if further study (a RCT) is justified.
Systemic sclerosis (SSc, Scleroderma) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. There is no effective treatment for the majority of patients with diffuse scleroderma (diffuse cutaneous systemic sclerosis; dcSSc). Only few therapies have shown modest benefits in regard to some specific organ pathologies. In the early stage of dcSSc, it may be possible to reverse inflammation and reduce the probability of irreversible fibrosis via significant immune modulation as later, often the fibrosis doesn't improve with treatment. This is a pilot study that will treat 15 participants with dcSSc who meet the eligibility criteria. The objective of the study is to determine if the benefit of Extracorporeal photopheresis (ECP) and safety are favorable in order to consider and help in the design of a randomized controlled trial (RCT). This is a Phase II study that is uncontrolled and patients will remain on their background immunosuppressive treatment unless if contraindicated for safety or drug interactions. The trial is powered to show a mean change in skin thickness measured with modified Rodnan skin score (mRSS) of ≥5 over one year, in an uncontrolled, unblinded study. The Health Assessment Questionnaire Disability Index (HAQ-DI), patient and physician global scores, inflammatory markers, and combined response index in SSc (CRISS) will all be exploratory outcomes. Other outcomes such as changes in cells on skin biopsies from baseline to end of the trial will be explored if the study is positive.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Drug Intervention using a medical device. The ECP device is already licensed in Canada. License No.7703. ECP treatment, using the drug UVADEX, will be given on 2 consecutive days every 4 weeks for a total of 26 treatment days (48 weeks).
The phase II aspect of the study refers to the drug, methoxsalen. Methoxsalen is being used off label from the currently approved indications in the monograph. The study is proposing to use methoxsalen in combination with with extracorporeal photopheresis for the treatment of diffuse cutaneous systemic sclerosis. Treatment will be given in addition to standard of care medications for SSc.
Rheumatology Clinic, St. Joseph's Health Care
London, Ontario, Canada
Change in skin thickness measured by modified Rodnan Skin Score
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Time frame: 48 weeks
Change in the modified Rodnan Skin Score
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Time frame: 12, 24 and 36 weeks
Combined Response Index in diffuse cutaneous systemic sclerosis score
CRISS score: It is calculated according to changes from the start of a study, compared to an endpoint, by using the modified Rodnan Skin Score (mRSS), the Health Assessment Questionnaire - Disability Index (HAQ-DI), patient and physician global assessment of scleroderma-related health, and forced vital capacity. A CRISS score of ≥ 0.6 indicates likelihood that a patient improved on treatment. Will be calculated with baseline data and to define disease progression at 6 months.
Time frame: 24 weeks
Change in Forced Vital Capacity
Change in Pulmonary Function as measured by percentage of Improving or worsening FVC. The FVC (Forced vital Capacity) is the total amount of air exhaled during the FEV (Forced expiratory volume) test.
Time frame: 6 and 12 months
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Change in the diffusing capacity for carbon monoxide
Change in Pulmonary Function as measured by percentage of Improving or worsening DLCO. The DLCO (diffusing capacity of the lungs for carbon monoxide) measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries.
Time frame: 6 and 12 months
Change in physician global assessment of disease activity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease activity and 10 being the worst possible disease activity.
Time frame: 12, 24, 36 and 48 weeks
Change in physician global assessment of disease severity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease severity and 10 being the worst possible disease severity.
Time frame: 12, 24, 36 and 48 weeks
Change in physician global assessment of disease damage
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease damage and 10 being the worst possible disease damage.
Time frame: 12, 24, 36 and 48 weeks
Change in patient global assessment of health status
Measured on a Visual Analogue Scale (VAS) from 0-100, with 0 being no overall effect of disease on participant, and 100 being the worst possible overall effect of disease on participant. This is a patient reported outcome.
Time frame: 12, 24, 36 and 48 weeks
Change in Scleroderma Health Assessment Questionnaire
The SHAQ combines the disability and pain scales of the HAQ (HAQ-DI), with five scleroderma-specific Visual Analogue Scales for: digital ulcers, Raynaud's phenomenon, gastrointestinal (GI) symptoms, lung symptoms, and overall disease severity. The HAQ-DI yields a score of 0-3, that indicates the extent of the respondent's functional limitations. Each VAS score is scaled from 0 to 3, with 0 being no symptoms and 3 being the worst possible symptom severity. A composite VAS score is not created nor are the individual VAS scores incorporated into the HAQ DI score. Typically, each VAS score is reported individually. There is a proposed way to obtain a combined score obtained by pooling the 8 domains of the HAQ DI and the 5 VASs; however, this approach has not yet been widely accepted. This is a patient reported outcome.
Time frame: 12, 24, 36 and 48 weeks
Change in serum concentrations C-Reactive Protein
Change in serum concentrations of the acute phase reactant, CRP CRP aids in the evaluation of stress, trauma, infection, inflammation, surgery \& associated diseases. Blood levels of C-Reactive Protein (CRP) are known to rise in acute disease to a level of up to 50 mg/L in the presence of slight to moderate inflammatory process. Values \>50 mg/L indicate high and extensive inflammatory activity.
Time frame: 12, 24, 36 and 48 weeks
Change in serum concentrations of Erythrocyte Sedimentation Rate
Change in serum concentrations of the acute phase reactant, ESR Reference ranges: Male: 0-10 mm/h Female: 0-20 mm/h A faster-than-normal rate may indicate inflammation in the body. Inflammation is part of the immune response system. The higher the number, the higher the likelihood of inflammation.
Time frame: 12, 24, 36 and 48 weeks