Open Label Treprostinil Raynaud's Study

Phase 4Not Yet RecruitingNCT07112183

Brigham and Women's Hospital30 enrolled

Overview

Raynaud's phenomenon is a condition where the blood vessels in participants fingers and toes get too narrow when cold or stressed. This makes participants fingers and toes change colors - they might turn white, then blue, and finally red as blood flow returns. It can be painful and cause numbness or tingling. When participants have Raynaud's, blood vessels react too strongly to cold or stress. Fingers and toes may turn white (blood moves away from the area), blue (lack of oxygen), or red and feel painful or tingly when warming up. These episodes usually last from a few minutes to several hours. There are two types of Raynaud's. Primary Raynaud's (also called Raynaud's disease) itself and isn't connected to other health problems. It's the most common type and affects mostly women under 30. Secondary Raynaud's (also called Raynaud's phenomenon) is caused by other diseases like lupus, scleroderma, or rheumatoid arthritis. This type tends to be more serious and may cause painful sores on fingertips called digital ulcers. For mild cases, staying warm might be enough. But if symptoms are severe, participants doctor might prescribe various medications including calcium channel blockers - blood pressure medicines that help open blood vessels, or other vasodilators - medicines that widen blood vessels. About 40% of people with scleroderma develop painful sores on their fingertips called digital ulcers. These happen when there isn't enough blood flow to heal small injuries. For severe cases with digital ulcers, doctors might use prostacyclin therapy - medicines that mimic a natural substance that opens blood vessels. Oral treprostinil is a newer pill form of prostacyclin therapy that helps improve blood flow. The investigators are conducting a research study testing whether oral treprostinil - a pill that mimics prostacyclin (a natural blood vessel opener) - can help people with severe Raynaud's that doesn't respond to usual treatments. This represents hope for better treatment options for people with the most challenging cases of this condition.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

Interventions

Oral treprostinil (UT-15C) sustained release tabletsDRUG

30 patients with symptomatic primary or secondary Raynaud's phenomenon (RP) resistant to standard vasodilatory therapy will be enrolled. Prior to treatment, subjects will record each day for 42 days the number of RP attacks as well as the duration of each RP attack, considered to be baseline data. After the 6-week baseline run in, all subjects will receive oral treprostinil sustained release tablets. Dose escalations can occur every 48 hours in 0.125 mg increments. Subjects will be titrated as tolerated to a goal dose of 3mg three times daily over a 6-week period. Titration can be done as quickly as tolerated. Once at goal dose subjects will enter the 26-week treatment phase. Throughout the study (6-week titration - 26-week treatment phase) subjects will record each day the number of RP attacks.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria:• * Patients aged ≥ 18 years * Active Raynaud's Phenomenon defined as patients with refractory RP having four or more RP attacks per week in the 4 weeks before inclusion in the study despite stable background vasodilator treatment for at least 3 months. * Patients with primary Raynaud's Phenomenon * Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria. * Patients on stable dose phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers defined as 3-months with no change in dose will be allowed to participate. Exclusion Criteria: * Uncontrolled hypertension, diabetes mellitus, acute coronary or cerebrovascular event within 3 months, evidence of malignancy, history of sympathectomy * Smoking within 3 months or smoking cessation using nicotine products * Subjects with history of diverticulosis * Subjects with moderate to severe liver disease, Child Pugh Class B or C * Subjects currently taking any other prostacyclin. * Pregnant or breast feeding or considering pregnancy in next 4 months * Participation in trial with an investigational drug within 30 days

Outcomes

Primary Outcomes

Change in the Raynaud's Condition Score from baseline (6-week run in), comparing treprostinil treatment phase vs. baseline phase.

Once enrolled, throughout the study (6-weeks before active treatment; 6-week titration; 26-week treatment phase) subjects will record each day the number of RP attacks as well as the duration of each RP attack.. Frequency and duration of RP recorded within 6-weeks before active treatment phase will be considered to be baseline data. Every day subjects will complete the Raynaud's Condition Score (RCS). The RCS is an 11-point numerical rating scale (0-10) where 0 = "no difficulty" and 10 = "extreme difficulty". Patients complete the scale daily, and the average scores are calculated. The scale asks patients to consider multiple factors when rating their difficulty, including the number and duration of Raynaud's attacks, symptoms such as pain, numbness, burning, and tingling, and how the condition affects their ability to use their hands and perform daily activities.

Time frame: 38 weeks

Secondary Outcomes

Digital Ulcer Score

Digital Ulcer Score (DUS) will be assessed at every 4-week visit, Weeks 4, 8, 12, 16, 20, 24 and 28. Minimum Value: 0; No theoretical maximum. Higher scores indicate worse outcomes (more severe digital ulcers). The DUS is calculated by assessing each individual ulcer and multiplying the depth of the ulcer (1 point for hyperkeratosis, 10 points for ulcer) by the diameter (1 point if \<0.5 cm, 2 points for ≥0.5 cm). The total score is then calculated as the sum of all individual ulcer scores.

Time frame: 32 Weeks