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Systemic sclerosis (SSc) (scleroderma) is a rare autoimmune disease that affects about 84,000 individuals in the United States, with approximately 7,000 new cases diagnosed each year. Of all the rheumatological conditions, scleroderma has the highest mortality rate, along with many debilitating morbidities across the spectrum of SSc manifestations.
The most common feature of scleroderma, and the one that affects patient quality of life the most is Raynaud's phenomenon (RP). RP affects close to 95% of scleroderma patients and is characterized by constriction of the blood vessels in the digits in response to cold temperatures or stress. Among other complications of scleroderma-associated RP, patients can develop digital ulcers, compromising their quality of life. At present, there are no approved drug therapies to treat RP.
Robyn T. Domsic, MD, MPH, associate professor of medicine in the Division of Rheumatology and Clinical Immunology and clinical director of the UPMC Scleroderma Center, has an extensive research and clinical trials history investigating SSc. Overall, Dr. Domsic is interested in improving patient quality of life improve disease management. She has focused on creating and stratification strategies for scleroderma patients to improve patient care and clinical trial design. Another main area of Dr. Domsic’s research is RP and the vascular manifestations of scleroderma. Specifically, she is interested in novel imaging techniques for vascular involvement in scleroderma and assessing new outcome measures for testing therapies to manage RP. Her research priorities are at work in two current clinical studies highlighted here.
In 2019, Dr. Domsic received a $1.5 million grant from the Department of Defense Congressionally Directed Medical Research Program (DOD-CDMRP), to lead a three-center collaborative effort with Johns Hopkins University and the Royal National Hospital for Rheumatic Diseases in Bath, UK. The study, Optimizing Patient-Reported and Vascular Outcome Measures in Systemic Sclerosis-Associated Raynaud Phenomenon, is designed to elucidate a number of knowledge gaps related to systemic sclerosis and RP to spur the search for new drug therapies.
Specifically, the study has four areas it will probe. The first is the best way to measure a patient's RP attack frequency and severity, and the second deals with what ought to be used as patient-reported outcomes.
“A question we asked ourselves is why we do not as yet have any FDA-approved therapies to address RP. Is it because we do not have effective drugs, or is it the case that the measures we use to examine outcomes with respect to RP are not helpful or useful? If the latter is the case, could we develop both new functional measures to gauge improvements in blood flow but also derive better or more meaningful and accurate patient-reported outcomes measures,” says Dr. Domsic.
The study also examines optimal methodologies to measure vascular function and blood flow in the skin when researchers are testing new drug therapies.
Using advanced vascular imaging tools including a laser speckle camera and infrared thermography, Dr. Domsic’s study examines participants skin, blood flow, and warmth – warmth being used as a surrogate for blood flow – while patients are subjected to various challenges – cold challenges and ischemic challenges – that can mimic real-world patient experience and help to assess vascular health and function. More recent understandings in how scleroderma damages small blood vessels and the possible relationship between RP is the rationale for examining participant small vessels for functional parameters.
"Our study also is powered to answer the question of whether RP severity is affected by seasonal changes. To answer this question, our study follows patients for one year to capture the full spectrum of seasonal changes in ambient temperature,” says Dr. Domsic.
Patient recruitment for this study continues. The ultimate goal is to enroll 160 participants who will be followed for one year, with reporting and vascular testing conducted every three months. In addition, Dr. Domsic’s study is recruiting another cohort of 400 individuals to obtain information to refine and validate the new patient-reported outcomes questionnaire.
"We had to adjust our timing and methodologies somewhat because of the coronavirus pandemic, but we are again conducting the vascular studies with new patient and research safety parameters in place to mitigate contact and potential spread of the virus. Conducting research during this time has been challenging, but we are moving forward," says Dr. Domsic.
Fatigue and accompanying diminished activities of daily living are a common symptom experienced by patients with SSc that affects their quality of life. Previous studies have shown that about 75% of SSc patients experience fatigue, and more than half indicate it to be in their top three complaints of distress associated with the disease.
Chronic fatigue in SSc patients is linked to higher rates of depression. SSc patients with intractable fatigue also have difficulty sleeping, which can further exacerbate other symptoms and decrease quality of life.
“We have few therapeutic options to treat a patient’s fatigue if we can identify an underlying cause. If we cannot, then our options are even more limited to attempting cognitive behavior therapy or prescribing an exercise regimen to see if we can improve a patient’s experience of fatigue,” says Dr. Domsic.
To try and break through the treatment wall for SSc patients experiencing fatigue, Dr. Domsic and collaborators are engaged in a pilot study that employs a wearable device patients can place around their wrist or ankle that delivers wave-like vibrations to the user that can modulate or influence a person’s autonomic nervous system tone.
The device, from Apollo Neuroscience, was created by former University of Pittsburgh Department of Psychiatry and Neuroscience faculty member David, Rabin, MD, PhD, who developed the technology based on his research treating chronic stress.
“The device is completely noninvasive and user-controlled. The study participants have full control over when and how to use the device in relation to their experience of fatigue. They install an application on their smartphone that they use to control the wearable device,” says Dr. Domsic.
Because of the current situation with the COVID-19 pandemic, the entire study is being conducted remotely. Study participants are enrolled remotely, and interactions for device training, follow-up, technical problems, and recording of patient-reported outcomes measures are all done electronically – via phone, video, or internet.
Participants are enrolled in the study for a four-week period in which they wear the device and use it as they see fit. Participants in the pilot study continue taking any prescribed medications or other therapies as indicated while using the Apollo device.
"At the beginning of the study, we obtain a fatigue score for each person using the PROMIS fatigue scoring tool. We are enrolling only those individuals with at least a moderate fatigue score as indicated with PROMIS. At the end of the study, we obtain a second measurement using the PROMIS fatigue scale (and other scales), and we will then make comparisons,” says Dr. Domsic.
The pilot study is designed to provide preliminary data on patient tolerability of using the device and efficacy through PROMIS scale findings.
"This is a novel approach, one that is noninvasive and patient-controlled. We are hopeful we will see promising results, but much more research is needed beyond our pilot study to show efficacy. In the long-term, even if a therapy like this only benefits a small percentage of patients, it will be an incremental step in providing some relief to patients suffering from the debilitating effects of SSc. Time will tell," says Dr. Domsic.
For more information about Dr. Domsic’s research or clinical trials, please call 412-648-7871. Patient referrals for treatment may be directed to firstname.lastname@example.org as the preferred method of contact. Alternatively, the phone number for appointments is 412-647-6700.
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