HOPE for Managing Pain

Kidney disease is often invisible to other people until its late stages when dialysis – a process that filters wastes and extra water from blood – or a kidney transplant are required. Others don’t see the extreme fatigue, loss of appetite, nausea and dizziness, and leg cramps.

And others can’t see the terrible pain.

Some of this pain arises from the kidney failure itself, like bone pain. But other sources of discomfort, like nerve pain and vascular pain, may come from conditions that led to the kidney failure, such as diabetes, which is common in these individuals. And then there’s all the other kinds of pain unrelated to dialysis that are common to many of us and which dialysis patients experience too: arthritis pain, back pain, headaches, and tooth aches.

Given this high burden of pain, it may not be surprising that opioid use rates in people on dialysis are almost three times that of the general U.S. population over 65 – putting them at significant risk for addiction. A recent study reported that more than half of dialysis patients had one or more opioid prescriptions during any 12-month period, and 20% had prescriptions for more than 90 days. Use of opioids by individuals receiving dialysis or requiring dialysis has been linked to poor health outcomes, such as more hospitalizations, fractures, and deaths compared to those who don’t use opioids.

To help dialysis patients learn how to manage their pain safely and long-term, the Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®’s Hemodialysis Opioid Prescription Effort (HOPE) research study is testing various non-opioid treatment approaches in dialysis patients. This research, part of the initiative’s clinical research in pain management, aims to develop personalized treatments based on individual patient needs. To do that the researchers are meeting patients where they are by “bringing the trial to the participant.”

Meeting Patients Where They Are

Providing pain relief for these patients is very tricky, says nephrologist Laura Dember, M.D., of the University of Pennsylvania Perelman School of Medicine, Philadelphia.

“For many pain medications, the side effects are greater in people with kidney failure than in people with normal kidney function.”

Some pain medications, such as morphine, are difficult to use for people with kidney failure because their breakdown products build up and cause confusion or hallucinations. Other pain medicines, like ibuprofen and similar anti-inflammatory drugs, can cause gastrointestinal bleeding and also worsen already impaired kidney function. A few opioids do help with pain, but these drugs, such as oxycodone, can be addictive – as revealed by the high rates of opioid use in this patient population.

Chronic pain notwithstanding, just living with kidney failure and the need for dialysis is hard. Dialysis requires medical supervision and is done either in a hospital or medical clinic set up specifically for the purpose. In addition to doctors, staff that help coordinate patient care include nurses, technicians, social workers, dieticians, and nurse managers.

Many dialysis patients are on 10 or more medications and need to be very careful about what they eat so as not to throw off the delicate balance of metabolism maintained through the dialysis process. Social workers and other staff offer psychosocial support to people receiving dialysis as well as help with transportation and insurance coverage for the long list of medications they need to take, which insurance doesn’t always cover.

A typical patient goes to a dialysis unit three times a week for four-hour sessions. That means they’re stuck sitting in a dialysis chair, not able to get up and move, for 12 hours out of every week.

“Those three days are really just gone from their life,” says nephrologist Manisha Jhamb, M.D., M.P.H., of the University of Pittsburgh School of Medicine. “Their not-on-dialysis time is their precious time. Patients don’t want to go and see another doctor, and most do not want any more medications.”

Jhamb and Dember are part of a large team of researchers that includes nephrologists and specialists in pain management and addiction who are testing whether a non-medication approach to pain can help dialysis patients by taking advantage of their time in dialysis to offer pain treatment tailored to each patient.

“The whole idea is to meet patients where they are, whether at home or in the dialysis unit” explains Paul Kimmel, M.D. of the National Institute of Diabetes and Digestive and Kidney Diseases, who is overseeing the HEAL-funded study taking place at eight different clinical centers across the United States and coordinated by a data research center at the University of Pennsylvania.

The study, which began enrolling participants in late winter 2020, is a randomized trial that will look at the effectiveness of both non-medication and medication-based approaches for reducing pain and opioid use in dialysis patients. The researchers will work with patients during their dialysis time, or at their convenience, offering them pain coping skills training with a coach. Separately, they will also test a safer and less addictive form of opioid (buprenorphine) that is effective for treating pain.

Each research question will be tested in separate experiments, and about 640 patients overall are expected to participate.

To be sure that the research has the best chance at being successful (and its findings shared with others), patients were included in most stages of the research planning. Patients helped to choose the clinical outcomes to be measured and designed recruitment materials to attract study participants. Patient participants also serve as advisors at each clinical research site, so they have a say in decisions made that could affect the conduct of the trial.

Living Without Interference

For dialysis patients, pain intensity usually isn’t their biggest complaint, but rather how much the pain gets in the way of living life. Through other research, we already know that pain coping skills training can help. The basic principle is that an individual doesn’t need to be a passive victim of pain – but rather that changes in behavior, thoughts, and mood can put a patient in charge of handling his or her pain.

“As health providers, we know we might not be able to completely take away the pain, but we can hopefully bring pain down to a more manageable level by giving patients cognitive behavioral skills that improve their ability to participate in life and social activities,” explains Jhamb.

For this study, the researchers will use a psycho-educational approach widely in use for chronic pain, but that has not been tested for people treated with dialysis. A central pool of coaches with standardized training and ongoing oversight will be available for the coping skills training in two separate phases. For the first 12 weeks, patients will participate in weekly, 45-minute one-on-one telehealth sessions with a live coach. They will then get “booster” sessions of customized messages, coach feedback, and self-paced skill review for another 12 weeks.

Because finding a therapist – or using not-on-dialysis time to see one – can be barriers for people who need dialysis, the study is using a telehealth strategy using virtual therapy sessions accessible during dialysis treatment.

Other Options

After this first segment of the HOPE study testing the value of pain coping skills training, those patients in the study who continue to be taking significant doses of opioids, and do not have conditions that would be at odds with receiving buprenorphine, will be offered the drug as another approach for managing pain.

Although coping skills training is effective for learning how live with pain, medications are also useful if they are safe. Buprenorphine, for instance, is FDA-approved for pain and for treatment of opioid use disorder, and it is less likely to cause overdose and respiratory depression in people who have been taking chronic opioids. As well, blood levels of this medication remain stable, since it is not washed out by the dialysis process.

“But people fear that switching from their usual opioid medication will not treat their pain,” says addiction medicine specialist Jane Liebschutz, M.D., of the University of Pittsburgh School of Medicine and part of the HOPE research team.

Unfortunately, buprenorphine carries stigma like other medications used to treat opioid use disorder, such as methadone.

“And on top of that,” Liebschutz continues, “Individuals with chronic pain, and treated with dialysis, already experience negative judgement and misunderstanding of their symptoms and limitations.”

The second stage of the HOPE study will test whether buprenorphine is an effective alternative to other, stronger opioid medications, such as oxycodone, for dialysis patients. The researchers will use the type of buprenorphine covered by most insurance – so if the research is successful the drug will be easy for patients to obtain after the study is over.

As an extension of the HOPE study, Liebschutz and Jhamb are looking closely at how to combat buprenorphine stigma from various sources: not just from patients and their caregivers, but also from nephrologists, dialysis staff, and a patient’s primary care providers. This work is informing their development of a multi-level stigma intervention to encourage use of buprenorphine for pain relief in people treated with dialysis.

The HOPE study intends to answer key questions about how to help people treated with dialysis manage their pain and avoid use of opioids that can pose harm. The study aims to determine the most effective and efficient way for individuals to acquire coping skills, and to reduce stigma (and thus, increase use) of medications known to help provide pain relief that aren’t addictive.

The study team will look for other connections to help identify novel risk factors for pain and opioid use in people treated with dialysis. As such, the researchers will document co-existing conditions, such as diabetes and mental health disorders, as well as other factors like socioeconomic status, social isolation, social support, residential factors, and perception of racial discrimination. The scientists will also work to understand effects of non-opioid pain approaches on pain control, patient satisfaction with care, perception of quality of life, hospitalization rates, and mortality rates.

The HOPE study is very timely since to date, many interventions have not been tried in people receiving dialysis. This research provides an opportunity to reduce the rate of opioid prescription and opioid use, as well as help address related issues such as depression, anxiety, and pain. And the effort aims to do much more – not only prevent opioid misuse but also create a template for how research can address the needs of a whole person and help patients get back to living their lives.