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Risky tactic, desperate need: Trial to test brain implants for opioid addiction
By Max Blau
February 13, 2018
The arsenal of therapies available to combat opioid addiction has expanded1 beyond pills and shots to include over-the-ear electrodes and virtual reality headsets. But an upcoming clinical trial could push the boundaries of addiction treatment further, and by a more invasive means than any therapy currently embraced by medical experts.
The therapy, called deep brain stimulation, requires electrodes to be implanted into the brain to regulate activity in the brain’s neurons, much like a pacemaker does to the heart. Deep brain stimulation is currently used to treat tremors related to Parkinson’s disease, and is being tested on patients diagnosed with a variety of brain disorders.
Small studies have shown that DBS could counter addiction as well. A trial slated to start later this year could be the first in the U.S. to rigorously test it as a treatment for opioid addiction. But the therapy’s promise comes with a heavy caveat — the risk of brain surgery without solid proof of its effectiveness.
The trial is the brainchild of Dr. Ali Rezai, a 52-year-old neurosurgeon hired by West Virginia University to use brain science to battle the epidemic using a suite of new technologies. The state2 is home to the highest drug death rate in America. In response to pain pills engulfing coal-mining towns and fentanyl flooding its cities, politicians including West Virginia’s governor have held Rezai and his innovations up as a beacon of hope.
The trial stems from Rezai’s belief that “it’s time to be more aggressive” in combatting addiction. If DBS works, he said, it could help people who have been failed by other kinds of treatment.
“If there’s a condition that’s life-threatening like opioid addiction, we should explore this technology,” Rezai told STAT, “as long as it’s safe.”
It’s that last part that he’s hoping to figure out.
To place a DBS implant — something Rezai has done more than 2,000 times in his career — he makes a small, inch-long incision in a patient’s scalp. He drills a small hole into the skull no larger than a dime, and then inserts a tiny electrode that targets the nucleus accumbens, the region of the brain acting as its reward center. After that, he tunnels a wire beneath the skin to a battery implanted in the patient’s chest.
“You can use it like a pacemaker to reduce signals to the brain that lead to less anxiety — and the need for addictive behavior,” he said.
The implant accomplishes this goal by delivering pulses of electricity to the brain’s reward center in hopes of decreasing over-activity behind addictive behavior. Doctors can adjust how often the stimulation occurs, as well as how powerful the stimulation should be.
The trial that Rezai plans to start would, to his knowledge, be the first testing DBS for opioid addiction in the U.S. It aims to recruit a handful of volunteers for a start date of later this year.
After placing the implant, DBS can be turned off or adjusted, minimizing the risk of potential long-term harm to patients. Even still, Rezai tells patients who’ve received DBS for other conditions that there’s a 1 percent chance of a severe problem including the possibility of a stroke or infection. “I don’t think anyone can claim there’s no risk with DBS,” Rezai said.
And indeed, back in 2011, some researchers were warning that this risk made it irresponsible to test DBS as an addiction treatment. “Insertion of stimulating electrodes can cause serious infections and produce cognitive, behavioral, and emotional disturbances,” wrote7 addiction researchers Wayne Hall and Adrian Carter. “It can also produce irreversible psychosocial changes that can be harmful. … Evidence suggests that the very uncertain benefits of deep brain stimulation in alleviating the symptoms of addiction do not outweigh the known harms associated with the procedure, or the harm of not providing deep brain stimulation (on the assumption that other currently available treatments are provided to the highest standard).”
Because of this risk, researchers have struggled to recruit participants for similar trials in the past.
In 2010, Judy Luigjes, who studies DBS at the University of Amsterdam’s Academic Medical Center, launched an eight-person pilot DBS study for people addicted to either opioids or cocaine. But in the end she could only find two participants. The following year German researchers launched what was supposed to be a 10-person randomized clinical trial to study DBS on adults with long-lasting heroin addiction. According to ClinicalTrials.gov, they’re still in the recruiting phase, even though the study was supposed to wrap up last year. (The researchers didn’t respond to STAT’s requests for comment.)
“Recruitment was harder than expected,” Luigjes said. “We had a long screening procedure, hoping people weren’t deciding impulsively. Few wanted to go through with it. A lot of it has to do with fear of the procedure.”
At Shanghai’s Ruijin Hospital, neurosurgeon Dr. Bomin Sun launched a 20-person clinical trial to investigate DBS for opioid addiction in late 2016. In an interview with STAT, Sun said his team finished with fewer than 20 people who injected heroin, and are still looking at their findings. Based on the preliminary data, he said that more than half of the participants stopped taking the drugs for more than one year.
“But it’s hard to find the suitable patients,” Sun said. “Some patients are lost before the follow-up because they don’t want to do a follow-up or they disappear.”
Rezai’s forthcoming clinical trial will start small with just a handful of participants who have survived an opioid overdose and failed to quit using after multiple kinds of treatment. If the study is proven safe and effective enough, Rezai said the group will move forward with a larger trial in which half of the participants receive DBS through the implant and half get a sham device.
Rezai hopes he’ll be able to recruit enough participants. More importantly, he feels the need to recruit the right kinds of patients, including ones that won’t be likely to drop out of the trial — something that’s bogged down past research. Though Rezai hopes to move “slow and carefully” — with DBS for opioid addiction becoming widely available no earlier than 2025 — he may face pressure to catch up to other researchers seeking to get there faster.
Sun and his team at Ruijin Hospital are starting a new trial in which they, along with researchers at several other medical institutions, aim to recruit 60 subjects in five different cities across China. He told STAT the randomized study will employ a new kind of electrode to target both the nucleus accumbens and the interior limb of the internal capsule. Their goal is to have DBS implants for opioid addiction available to the public by 2022.
“We want DBS to replace an [opioid replacement therapy] like methadone. Then patients can become totally drug free,” Sun said. “There’s no doubt this could be a good alternative.”
At a recent town hall meeting at West Virginia University, Rezai lectured about the suite of experimental therapies he’s developing at the university’s new neuroscience institute to help people overcome opioid addiction. He spoke highly of non-opioid injections to relieve pain and wearable sensors that may help predict addictive behavior. And though he expressed some excitement about DBS for those with severe addiction, it was coupled with reservations, too.
“It’s very powerful technology,” he told the crowd. Still, “the goal in the future is to not need implants,” he said.
Rather, Rezai told STAT he’d like to see the development of therapies that don’t require drilling into the skull — things like transcranial magnetic stimulation, which harnesses magnetic fields to stimulate the brain’s nerve cells, and is currently being used to treat severe depression.
“You want to help patients, but not everything should be done surgically, if you can avoid it,” Rezai said. “We need to more toward becoming less and less invasive. If we can do that, we need to go after that.”
Risky tactic, desperate need: Trial to test brain implants for opioid addiction
By Max Blau
February 13, 2018
The arsenal of therapies available to combat opioid addiction has expanded1 beyond pills and shots to include over-the-ear electrodes and virtual reality headsets. But an upcoming clinical trial could push the boundaries of addiction treatment further, and by a more invasive means than any therapy currently embraced by medical experts.
The therapy, called deep brain stimulation, requires electrodes to be implanted into the brain to regulate activity in the brain’s neurons, much like a pacemaker does to the heart. Deep brain stimulation is currently used to treat tremors related to Parkinson’s disease, and is being tested on patients diagnosed with a variety of brain disorders.
Small studies have shown that DBS could counter addiction as well. A trial slated to start later this year could be the first in the U.S. to rigorously test it as a treatment for opioid addiction. But the therapy’s promise comes with a heavy caveat — the risk of brain surgery without solid proof of its effectiveness.
The trial is the brainchild of Dr. Ali Rezai, a 52-year-old neurosurgeon hired by West Virginia University to use brain science to battle the epidemic using a suite of new technologies. The state2 is home to the highest drug death rate in America. In response to pain pills engulfing coal-mining towns and fentanyl flooding its cities, politicians including West Virginia’s governor have held Rezai and his innovations up as a beacon of hope.
The trial stems from Rezai’s belief that “it’s time to be more aggressive” in combatting addiction. If DBS works, he said, it could help people who have been failed by other kinds of treatment.
“If there’s a condition that’s life-threatening like opioid addiction, we should explore this technology,” Rezai told STAT, “as long as it’s safe.”
It’s that last part that he’s hoping to figure out.
To place a DBS implant — something Rezai has done more than 2,000 times in his career — he makes a small, inch-long incision in a patient’s scalp. He drills a small hole into the skull no larger than a dime, and then inserts a tiny electrode that targets the nucleus accumbens, the region of the brain acting as its reward center. After that, he tunnels a wire beneath the skin to a battery implanted in the patient’s chest.
“You can use it like a pacemaker to reduce signals to the brain that lead to less anxiety — and the need for addictive behavior,” he said.
The implant accomplishes this goal by delivering pulses of electricity to the brain’s reward center in hopes of decreasing over-activity behind addictive behavior. Doctors can adjust how often the stimulation occurs, as well as how powerful the stimulation should be.
The trial that Rezai plans to start would, to his knowledge, be the first testing DBS for opioid addiction in the U.S. It aims to recruit a handful of volunteers for a start date of later this year.
After placing the implant, DBS can be turned off or adjusted, minimizing the risk of potential long-term harm to patients. Even still, Rezai tells patients who’ve received DBS for other conditions that there’s a 1 percent chance of a severe problem including the possibility of a stroke or infection. “I don’t think anyone can claim there’s no risk with DBS,” Rezai said.
And indeed, back in 2011, some researchers were warning that this risk made it irresponsible to test DBS as an addiction treatment. “Insertion of stimulating electrodes can cause serious infections and produce cognitive, behavioral, and emotional disturbances,” wrote7 addiction researchers Wayne Hall and Adrian Carter. “It can also produce irreversible psychosocial changes that can be harmful. … Evidence suggests that the very uncertain benefits of deep brain stimulation in alleviating the symptoms of addiction do not outweigh the known harms associated with the procedure, or the harm of not providing deep brain stimulation (on the assumption that other currently available treatments are provided to the highest standard).”
Because of this risk, researchers have struggled to recruit participants for similar trials in the past.
In 2010, Judy Luigjes, who studies DBS at the University of Amsterdam’s Academic Medical Center, launched an eight-person pilot DBS study for people addicted to either opioids or cocaine. But in the end she could only find two participants. The following year German researchers launched what was supposed to be a 10-person randomized clinical trial to study DBS on adults with long-lasting heroin addiction. According to ClinicalTrials.gov, they’re still in the recruiting phase, even though the study was supposed to wrap up last year. (The researchers didn’t respond to STAT’s requests for comment.)
“Recruitment was harder than expected,” Luigjes said. “We had a long screening procedure, hoping people weren’t deciding impulsively. Few wanted to go through with it. A lot of it has to do with fear of the procedure.”
At Shanghai’s Ruijin Hospital, neurosurgeon Dr. Bomin Sun launched a 20-person clinical trial to investigate DBS for opioid addiction in late 2016. In an interview with STAT, Sun said his team finished with fewer than 20 people who injected heroin, and are still looking at their findings. Based on the preliminary data, he said that more than half of the participants stopped taking the drugs for more than one year.
“But it’s hard to find the suitable patients,” Sun said. “Some patients are lost before the follow-up because they don’t want to do a follow-up or they disappear.”
Rezai’s forthcoming clinical trial will start small with just a handful of participants who have survived an opioid overdose and failed to quit using after multiple kinds of treatment. If the study is proven safe and effective enough, Rezai said the group will move forward with a larger trial in which half of the participants receive DBS through the implant and half get a sham device.
Rezai hopes he’ll be able to recruit enough participants. More importantly, he feels the need to recruit the right kinds of patients, including ones that won’t be likely to drop out of the trial — something that’s bogged down past research. Though Rezai hopes to move “slow and carefully” — with DBS for opioid addiction becoming widely available no earlier than 2025 — he may face pressure to catch up to other researchers seeking to get there faster.
Sun and his team at Ruijin Hospital are starting a new trial in which they, along with researchers at several other medical institutions, aim to recruit 60 subjects in five different cities across China. He told STAT the randomized study will employ a new kind of electrode to target both the nucleus accumbens and the interior limb of the internal capsule. Their goal is to have DBS implants for opioid addiction available to the public by 2022.
“We want DBS to replace an [opioid replacement therapy] like methadone. Then patients can become totally drug free,” Sun said. “There’s no doubt this could be a good alternative.”
At a recent town hall meeting at West Virginia University, Rezai lectured about the suite of experimental therapies he’s developing at the university’s new neuroscience institute to help people overcome opioid addiction. He spoke highly of non-opioid injections to relieve pain and wearable sensors that may help predict addictive behavior. And though he expressed some excitement about DBS for those with severe addiction, it was coupled with reservations, too.
“It’s very powerful technology,” he told the crowd. Still, “the goal in the future is to not need implants,” he said.
Rather, Rezai told STAT he’d like to see the development of therapies that don’t require drilling into the skull — things like transcranial magnetic stimulation, which harnesses magnetic fields to stimulate the brain’s nerve cells, and is currently being used to treat severe depression.
“You want to help patients, but not everything should be done surgically, if you can avoid it,” Rezai said. “We need to more toward becoming less and less invasive. If we can do that, we need to go after that.”
