Dr. Salmon and her team completed an observational study of 775 pregnancies to determine the strongest predictors of pregnancy complications in patients with lupus and/or APS. The presence of certain autoantibodies in women with APS with or without lupus is associated with a nearly 50% risk for serious adverse pregnancy outcomes. The IMPACT trial will determine whether treatment with Certolizumab, a monoclonal anti-TNF antibody that blocks inflammation, will prevent serious pregnancy complications. Studies in experimental animal models show that blocking this inflammatory mediator prevents preeclampsia, fetal death and fetal growth restriction – all problems seen in patients with lupus and with APS.

The grants from the NIH and Lupus Foundation of America come at a pivotal time in the study as they have recently enrolled 40 patients, and, so far, they are seeing promising results. The trial is spearheaded by the HSS Research Institute and University of Utah, where Dr. David Ware Branch serves study Co-Principal Investigator.  Patients across the nation are eligible to enroll in the trial. To do so, they or their physicians can contact Drs. Salmon or Branch.

Dr. Salmon, Co-Principal Investigator of the trial, said, “In addition to helping lupus and APS patients carry babies to term – a feat once deemed near impossible—we hope to eventually apply the results of our study to non-autoimmune patients at risk for preeclampsia, a life-threatening and common condition with no treatment.”

There is no proven treatment for COVID-19, but researchers around the globe are investigating different approaches that may help critically ill people recover. “Based on very small case studies, convalescent plasma is one of the more promising therapies that are currently available,” says Chad M. Craig, MD, MBA, FACP, an internal medicine specialist at HSS and primary investigator for the HSS site. “To help patients at our hospital and other hospitals in New York, we are asking our community members and any New Yorkers who have recovered after testing positive for COVID-19 to donate plasma through the New York Blood Center.”

Plasma is the clear portion of blood. It contains antibodies, small proteins that the immune system creates to defeat invading bacteria and viruses. People who recover from COVID-19 produce antibodies that recognize portions of SARS-CoV-2, the virus that causes COVID-19, and destroy it. “Infused antibodies attack the virus directly but also have indirect benefits that allow the body to create its own defenses to fight the infection,” says Dr. Craig.

Convalescent plasma has been tried as a treatment approach during other pandemics, including the Spanish flu of 1918 to 1920. During more recent outbreaks, researchers found it was beneficial against coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as H1N1 influenza.

Two studies in China earlier this year showed promising results for convalescent plasma in about 15 patients who were severely sick with COVID-19. Many improved shortly after receiving an infusion and had no severe side effects. However, this evidence was from a small number of patients.

The US Food & Drug Administration (FDA) recently approved the emergency use of convalescent plasma for patients infected with SARS-CoV-2 and outlined donor eligibility requirements. Donors must have a documented positive test result for the virus and cannot donate until at least 14 days have passed since the last day of experiencing symptoms.

Hospitals can seek approval from the FDA to use convalescent plasma on an emergency, case-by-case basis or by enrolling in expanded access programs. HSS has pursued both avenues for gaining access to convalescent plasma for eligible patients.

The expanded access program at HSS is part of a large national study led by the Mayo Clinic. Participation provides HSS with a more efficient way to access plasma on an ongoing basis for COVID-19 patients who are hospitalized and have a high risk of progressing to severe or life-threatening disease.

HSS suspended all nonessential surgeries on March 17, 2020 and made bed capacity, supplies and staff available to help neighboring hospitals. As the burden on the New York City healthcare system grew, HSS opened up over 200 beds and started receiving COVID-positive patients on April 1, 2020.

“At HSS, specialists with expertise in internal medicine, rheumatology, infectious diseases and critical care are working together to help patients who are hospitalized with COVID-19.” Dr. Craig says. “Convalescent plasma has the potential to shorten the severity or length of illness. We sincerely hope that this method will save lives, but we won’t know until we try.”

There is no cost to patients being treated with convalescent plasma as part of the program. Donating plasma involves the same process as donating blood and takes about 45 minutes. One plasma donation could potentially save the lives of up to four patients. If you are willing to donate, visit the New York Blood Center for more information and to submit a donor request form. 

For more information about the expanded access program, please contact Dr. Craig at craigch@hss.edu.

GCA, sometimes referred to as temporal arteritis, is the most common form of systemic vasculitis in adults. It typically occurs in people over age 50, with a peak in the mid 70s, and is more common in women than men. “HSS has a great history of being able to enroll vasculitis patients in clinical trials,” said Lindsay S. Lally, MD, a rheumatologist and trial co-investigator who serves as the site principal investigator at HSS. “HSS is one of the only places in the New York City area that has a dedicated vasculitis center, with physicians who have clinical and research expertise in diagnosing and treating these diseases. We have been at the forefront of a lot of the recent advancements in the understanding of giant cell arteritis, in terms of pathogenesis and treatment.”

GCA, an inflammatory autoimmune disease, is classified as a large vessel vasculitis (affects the large blood vessels of the scalp, neck and arms) but typically also involves medium sized arteries of the scalp, neck and arms, particularly the superficial temporal arteries—hence the term temporal arteritis. Inflammation causes a narrowing or blockage of the blood vessels, interrupting blood flow. The causes of GCA are uncertain. One of the most feared complications of the disease is vision loss or blindness.

For decades, the mainstay of treatment for GCA has been high doses of prednisone and other systemic glucocorticoid steroids, which work quickly to reduce inflammation but come with a host of potential side effects and toxicities. Many people with GCA are elderly and have other medical comorbidities, such as diabetes and osteoporosis. “Being on high doses of steroids for months can lead to worsening blood sugar control and elevated blood pressure and fractures,” said Dr. Lally. “More than 80 percent of patients will have some toxicity related to being on systemic steroids. What we have really tried to do as a vasculitis community is to explore other medications that can adequately control the inflammation, prevent blood vessel damage and end organ complications like blindness or strokes while minimizing toxicity to patients.”

One drug, tocilizumab, which was approved for GCA in 2017, has been effective in limiting the amount of steroids that some patients need, but it is not appropriate for everyone. “We still need to find other treatment strategies that can adequately control the inflammation while minimizing the amount of steroids that we expose patients to,” said Dr. Lally.

Mavrilimumab is a human monoclonal antibody that binds to the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha, inhibiting the GM-CSF signaling. “Granulocyte macrophage colony-stimulating factor is a chemical that should, in normal situations, be signaling for certain types of white blood cells to grow and expand,” said Dr. Lally. “We think that in giant cell arteritis, there are aberrations in this pathway. Certain types of white blood cells are present in higher levels and are more active, and that results in the inflammation that we see in the blood vessels. Data in preclinical models suggest that blocking this chemical may stop the proliferation of inflammatory cells in GCA.”

The clinical trial consists of a screening period of up to six weeks; a 26-week double-blind placebo-controlled period during which subjects receive blinded subcutaneous mavrilimumab injections weekly or placebo co-administered with a 26-week corticosteroid taper; and a 12-week washout safety follow-up period during which subjects no longer receive mavrilimumab or placebo and are transitioned back to standard of care. “The primary objective is sustained remission at week 26,” said Dr. Lally. “Endpoints include time to flare, sustained remission, and cumulative steroid doses. The goal is to see if patients can be on clinical remission, off of steroids, within 26 weeks.”

To be eligible for the trial, patients need to show evidence of active disease based on clinical symptoms and levels of inflammatory markers in the blood. “Patients also need to have hard evidence of the disease, which would either be a biopsy or ultrasound of the temporal artery, showing evidence of inflammation in that blood vessel, or an MRI or CT scan of the large blood vessels that shows evidence of active inflammation,” said Dr. Lally.

Female trial participants must be postmenopausal or permanently sterile following documented hysterectomy with bilateral salpingectomy, bilateral oophorectomy or tubal ligation; be nonpregnant or nonlactating and have a male partner with a vasectomy; or have agreed to use birth control if sexually active. Male subjects must have a documented vasectomy or, if sexually active, must agree to use a highly effective method of contraception.

Mavrilimumab has been previously studied in over 500 patients with rheumatoid arthritis. Dr. Lally will review the safety profile of mavrilimumab with patients who qualify for this study. Patients will be followed very closely for any potential side effects.

According to Robert F. Spiera, MD, director of the Vasculitis and Scleroderma Program at HSS, there is a heterogeneity to large vessel vasculitis. “This trial targets a mechanism that we would expect to be relevant to these disorders,” he said. “We continue to strive to help develop better therapies and are excited to have this trial available to our patients."

For information on how to enroll in the trial at HSS, call 646-797-8443.

Tendons connect muscles to bone, allowing the body to move. They respond and adapt to the demands of specific activities such as walking, running or playing sports. For example, leg tendons become more spring-like in basketball players, allowing them to jump higher and with more explosive force. Tendon injuries such as Achilles tendon rupture can occur through overuse or repetitive strain and are common among athletes.

“Ruptured tendons can be catastrophic. About 30 percent of athletes with an Achilles tendon rupture are not able to return to play, and those who do return regain about 75 percent of their pre-injury ability,” said senior author Christopher Mendias, PhD, ATC, an associate scientist in the Orthopaedic Soft Tissue Research Program at HSS. “There has been a lot of discussion in the NBA and other professional sports leagues about the recent increase in Achilles tendon ruptures and tendon injuries. We are also seeing an increase in tendon ruptures in the general population.”

In the basic science study, published September 19, 2019, in The FASEB Journal, the HSS researchers used advanced genetics techniques to remove the IGF1 gene in cells and then monitored tendon growth. They found that without IGF1, tendons were smaller and didn’t adapt like they normally would.

Next, the researchers added IGF1 to tendon cells in culture to study precisely how IGF1 affected the cells’ growth processes. “Two of the ways that IGF1 affected tendon cells was through increasing cell division and stimulating the synthesis of new proteins.,” said first author Nathaniel Disser, BS, a research fellow at HSS. Making new protein, such as collagen, is an important process the body uses to form tendons and other connective tissues.

In humans, growth hormone drives childhood growth and helps preserve tissues throughout adult life by maintaining adequate IGF1 levels. Human growth hormone (somatropin) is already available by prescription for treating children with growth failure due to growth hormone deficiency or adults with growth hormone deficiency. There is also another available drug called mecasermin (Increlex), which is a form of IGF1. It is used to treat children with a severe growth hormone deficiency, such as the absence of a gene to produce growth hormone.

“Overall, our study has identified that IGF1 plays an essential role in tendon growth and paves the way for future research to test whether targeting IGF1 is useful for treating painful and debilitating tendon injuries,” Dr. Mendias said. “Clinical trials are required before drawing conclusions about the ability of human growth hormone to repair tendon injuries better than is possible today.”

Dr. Mendias and colleagues are also currently completing a clinical trial testing the ability of human growth hormone to increase IGF1 levels to see whether that may prevent muscle atrophy in people recovering from anterior cruciate ligament (ACL) tears.

The rotator cuff is a collection of muscles and tendons at the shoulder joint that allows it to move. Overuse from repetitive overhead activities like swimming, tennis, or pitching a baseball, or acute injuries, can cause tears in the muscles or tendons of the rotator cuff.

“Arthroscopic shoulder surgery for rotator cuff tears is effective for relieving pain, restoring function and improving quality of life, but up to 25% of patients show incomplete or failed healing on imaging,” says Dr. Rodeo. “The frequency of incomplete or failed healing is more pronounced in patients over the age of 60. That matters because more people today want to stay active as they age.”

Many tissues in the body, including muscles and tendons, harbor stem cells that have the ability to form new tissues. The new clinical trial will test whether injecting an experimental cell therapy into both the muscle and the tendon of an injured rotator cuff will stimulate stem cell activity and promote better repair.

The engineered cell therapy product is E-CEL UVEC®, produced by San Diego based Angiocrine Bioscience, Inc. The investigational product consists of endothelial cells derived from the walls of the blood vessels of human umbilical cords that have been genetically modified to maintain their stability and their regenerative properties. The US Food and Drug Administration has granted the cell therapy Investigational New Drug (IND) status.

In a previous basic science study led by Dr. Rodeo, the cell therapy showed accelerated healing and an increase in the strength of the tendon attachment at the repair site, with no observable side effects, compared to surgery alone.

In the new clinical trial, patients with full-thickness rotator cuff tears who undergo arthroscopic surgical repair will receive two injections of the cell therapy: one into the tendon and one into the adjacent muscle. The study is open-label, meaning that all volunteers will know that they received the cell therapy.

The primary objective of the trial is to evaluate the safety of the cell therapy over 12 months. Dr. Rodeo and his research team will use blood tests to check whether the experimental cells have migrated away from the rotator cuff repair site. The investigators will also evaluate patients’ symptoms as well as shoulder strength, motion and healing as measured by MRI, ultrasound and patients’ reports about their progress.

“Improving patients’ symptoms with standard rotator cuff surgery is good, but strength improvements are less predictable,” Dr. Rodeo says. “Identification of new ways to improve healing and muscle function would represent a significant advance in the treatment of rotator cuff tendon tears.”

“We continue to enjoy working with Dr. Rodeo and his team on this long-term collaborative effort and look forward to providing support for this exciting new therapeutic application of E-CEL UVEC cells,” commented Paul Finnegan, MD, Angiocrine’s CEO.

The study opened September 1, 2019, with the goal of recruiting up to 20 patients ages 45 to 70 with full-thickness rotator cuff tears confirmed by physical examination and MRI. Eligible participants must already have tried and failed standard non-operative approaches, including a minimum of three months of physical therapy, oral anti-inflammatory medications, or a steroid injection.

For more information about the clinical trial (NCT04057833), please contact Camila Carballo, PhD, at carballoc@hss.edu or Daniel Edon, MS, at edond@hss.edu.

The multicenter Calypso Study will assess the safety and effectiveness of Moximed’s implantable shock absorber for the knee.  Moximed is a medical device manufacturer based in Fremont, California and is the sponsor of the study.   

The trial will enroll 80 men and women with medial knee OA, a painful, debilitating condition in which the cartilage barrier separating the ends of the femur and tibia deteriorates, allowing the two bones to rub against each other. Medial knee osteoarthritis can result from a variety of factors, including advanced age, the loss of estrogen after menopause for women, wear-and-tear from physical activity or obesity, and previous trauma to the joint, such as a torn ligament or meniscus. According to the CDC, an estimated 1 in 4 Americans suffer from some form of OA, and half are under the age of 65. 

Knee replacement surgery is an option for patients with medial knee osteoarthritis, but the procedure is relatively invasive and requires protracted recovery and rehabilitation. As a result, many patients opt for conservative care, which can entail the use of analgesics for pain, physical therapy and special insoles for shoes to help rebalance the affected joint—none of which prevent arthritis from progressing. 

"Many patients were injured when they were young, for example with anterior cruciate ligament (ACL) and meniscal tears, and these unfortunately lead to osteoarthritis in approximately 50% of them by 10 years after injury," said Andreas Gomoll, MD, sports medicine surgeon at HSS. "Since the original injury happens when patients are in their teens or 20s, they might have established osteoarthritis in their 30s and 40s, when knee replacement is not a great option since it has a high likelihood of wearing out during their lifetime and will have to be revised. Not surprisingly, doing a revision replacement is not as good as a primary replacement, and therefore we are looking for ways to delay these types of more invasive procedures for as long as possible. For some, conservative care helps, but not for everyone. That's where a device like the Calypso could fit in. If patients can buy years of improved pain and function, then knee replacement surgery can start later, requiring fewer possible revisions in the patient's lifetime. This device design is all about preserving options, since it can be removed with little-to-no permanent changes to the knee joint structure. Therefore, patients remain candidates for any other potential treatments that might be developed in the future."

The Calypso Study investigational device consists of a cylindrical shock absorber that is implanted along the side of the knee and reduces the amount of weight supported by the knee. 

"Nobody can wear a brace all the time for any length of time, and that's the advantage of an implantable device like Calypso," Dr. Gomoll said. "There is no other device like it and it offers a new approach for these patients."

"We are constantly pushing the biological envelope to preserve joints as long as we can," said Anil Ranawat, MD, sports medicine and knee joint preservation surgeon at HSS. "When a patient is young and has OA, it’s hard to know what the best procedure is. Injection therapy can relieve pain, but treatment benefit is only short term. More invasive surgical procedures, though effective in treating osteoarthritis, can inhibit treatment options down the road for young, active patients. The Calypso implant’s unique design maintains the anatomical structure of the knee while also treating the primary pain generator of OA. Our ultimate goal is to preserve motion and function in our patients."

The implantation surgery takes approximately one hour and can be performed on an outpatient basis, meaning patients can go home the same day. Rehabilitation is easier than for other knee surgeries, Dr. Gomoll noted.

The study will measure improvement over 24 months in pain and function based on a validated measure called the Western Ontario and McMasters University Osteoarthritis Index (WOMAC). The researchers also will track device safety and monitor the integrity of the implant over time using x-ray imaging. 

To participate in the study, patients must be between the ages of 25 and 65 and have had osteoarthritis pain on the inner side of the knee that has persisted for at least six months after trying non-surgical treatments. 

Patients are not eligible for the study if they have osteoarthritis in both sides of the same knee; if they have problems with the ligaments in their affected joint; if they have known allergies to certain metals; if they have been diagnosed with conditions that afflict the skeleton, such as rheumatoid arthritis and Paget’s disease; among other considerations.   

Two sports medicine surgeons at HSS are participating in the study: Andreas Gomoll, MD, and Anil Ranawat, MD.