December 10, 2013 in Features, Health

Clinical trials offer potential help for mentally ill while advancing drug development

By The Spokesman-Review
 
Colin Mulvany photoBuy this photo

Dr. John Tran is medical director of Frontier Behavioral Health and principal investigator at the Frontier Institute.
(Full-size photo)

For information

 To learn more about clinical trials at the Frontier Institute, call (509) 458-2405.

 Research is crucial for treatment and eventual cures of serious brain disorders, the National Alliance on Mental Illness says.

 At the same time, NAMI warns, participating in research could put volunteers at risk.

 The organization advises potential trial volunteers to fully understand the projects they’ll participate in – and to make sure they know the answers to some key questions before entering any studies:

• What is the study about?

• What will you be asked to do in the study?

• What risks might you face?

• Who do you contact with questions, concerns or problems?

• How will you be kept informed about the progress and results of the study?

The placebo group

 If there’s an existing treatment for the disorder being studied, clinical-trial rules limit the length of trials that give some patients placebos rather than real drugs.

 The idea is to limit the time sick people go without medication.

 But some mentally ill clinical-trial participants who receive placebos seem to get better, even without the benefit of pharmaceuticals, said Dr. John Tran, principal investigator at the Frontier Institute.

 In tests of drugs to treat depression, around 15 to 20 percent of participants experience a placebo effect, he said.

 For those patients, “breaking the blind” even after the trial can pose some danger, Tran said – essentially messing with their minds.

 “How does that affect you psychologically?” he said. “You’re like, ‘Oh, OK, am I faking my disease, or is there something else wrong?’ ”

 Instead, Tran said, the support a participant receives during the course of a trial can improve their mental health.

 A patient with severe depression might not have left their room for months. But after enrolling in a clinical trial, they have to shower, get dressed, eat, leave their home, interact with people.

 “Many of those interactions are important for recovery – not just the medication itself,” Tran said.

 That’s one reason it’s important to include a placebo group in clinical trials, he said – to “cut out all that extra effect” from the test results.

Adrian Rogers

Diagnosed with manic depression, now known as bipolar disorder, as a teenager, Charles Webb has been prescribed many pharmaceuticals and experienced many of their effects.

He knows what he feels like when they’re not working: way up and way down, he explained in a small room last week at the Frontier Institute near downtown Spokane, where he’s undergoing a clinical drug trial. He made a roller-coaster motion with his hand. Or – when he’s been prescribed depressants – sometimes he feels too sleepy, or as if the world has gone slow-motion.

“If you can, you want to go like this,” Webb said, drawing a smooth line in the air with his hand, “just like everybody else does.”

Three months into the yearlong trial at Frontier, Webb, a 54-year-old Spokane resident, said he’s felt his mental health improving. Trading in a regimen of 14 pills a day, with some required once a day and others twice or three times, he now receives just one medication, delivered monthly via an injection in his thigh.

The trial – conducted for Otsuka Pharmaceutical Co., maker of Abilify – is among about 20 a year conducted at the research division of Frontier Behavioral Health, formerly called Spokane Mental Health. Frontier Behavioral Health is the lead service provider in Spokane County’s public mental health system.

The institute is always recruiting participants with mental illnesses. Volunteers can benefit from the drugs being studied, help in the development of treatments that could help other people – or help establish that treatments don’t work, “so people are not being misled,” said Dr. John Tran, the institute’s principal investigator and medical director at Frontier Behavioral Health.

“The medicines that are on the market right now wouldn’t be available if not for the people who came before,” added Melissa Hampton, the institute’s trial operations manager.

The research institute – the only one of its kind in the area – draws on the pool of Spokane-area residents suffering from mental illnesses to test treatments, mostly for pharmaceutical companies. It uses roughly 100 to 150 new participants a year in trials ranging in length from a few weeks to a couple of years.

They’re people suffering from disorders including schizophrenia, Alzheimer’s disease and dementia, and bipolar disorder.

“Depression and GAD – generalized anxiety disorder – have been huge lately,” Hampton said. “With the health care system the way it is and people unemployed and out of work and no insurance, unfortunately in Spokane we can run an ad for depression and generate a lot of interest in it.”

Alternative route

That’s partly why the institute exists, say the people who run it – to provide care to people who couldn’t or wouldn’t otherwise get it, including working poor people with mental illness who don’t qualify for government help but can’t afford private insurance.

But it’s not only a lack of mental health coverage that compels residents to respond to TV and radio ads seeking study participants.

Some have received treatment in the past that hasn’t worked. Others seek a sense of control over their own health that they don’t get elsewhere, Hampton said.

Others, including those with good coverage or enough money to pay for care, seek the anonymity available through the institute, which doesn’t bill insurers, Tran said.

The people who run clinical trials aren’t supposed to call what they offer “treatment,” because that implies participants will necessarily get better, and they might not. Some people do receive placebos.

But, besides reaching people who can’t find help elsewhere, the institute aims to bring new “more advanced treatment modalities” to the Spokane area, Tran said.

For example, Frontier is testing a medication to treat cognitive impairment in people with schizophrenia that’s not otherwise available. It’s studying another drug to treat Alzheimer’s patients who have agitation – a group of behaviors including irritability, anxiety, sleep disturbances and pacing for which there’s no medication approved by the Food and Drug Administration.

And the institute recently finished a study on a medication to stop the involuntary movements – tardive dyskinesia – suffered by some patients as a result of the antipsychotic medications they might take for schizophrenia or bipolar disorder. “Up to now, there’s no treatment for that condition,” Tran said.

For Webb, who arrived at the Frontier Institute after seeing a TV ad, the monthly dose of Abilify in his thigh is a modality he can get behind. That’s despite his risk of skepticism when offered a new drug, he said, “because I’ve been told many times, ‘Take this one. This’ll work.’ ”

It’s not a “flat” feeling Webb is after – he still wants to feel happy and sad. And he knows there’s no cure for bipolar disorder. It’s control he’s after: to feel like himself. His manic episodes could last from a couple of hours to days.

“When I’m manic, it’s not me,” Webb said. “It’s like somebody took me out of the picture.”

Close monitoring

Through the contracts it signs with drug developers, the institute aims to generate revenue for Frontier Behavioral Health, Tran said, boosting funding for its public programs. Since the institute’s founding in 2009, that revenue has fluctuated by year and has yet to make a significant difference to the mental health system, he said.

But Tran said he’s seen trial participants with mental illness get better.

And they stand to receive close oversight of their mental condition along with any drug side effects, he said.

“Definitely the visits are much more frequent than you would get in a clinic, because typical clinic visits usually are either one a month or two months or three months, even for folks who are chronically mentally ill or in pretty severe condition,” Tran said. “Here, with many of the protocols, we have to monitor their condition much more closely.”

Significant bad effects of the patient’s participation in the trial – “adverse events” – must be addressed immediately as called for in trial designs, as approved by the FDA and the panels known as institutional review boards that approve and monitor research involving human subjects.

When a participant fares well during a trial, Frontier doctors can make recommendations for follow-up treatment to the patient’s primary care doctors.

‘You’re not stuck’

Those recommendations, however, come with a caveat: In double-blind studies, not even the doctors know for sure whether the study participant received a real drug or a placebo.

That’s a concern for patients and doctors, Tran said. Some patients with real illnesses could be forsaking real medication for what turns out to be a sugar pill.

That’s why in the U.S., he said, trials are limited to six months or less if there already is an existing treatment for the disorder.

Still, the National Alliance on Mental Illness counts studies with “placebo arms” among those requiring especially careful assessment before participants decide to enter. Others are trials that require participants to stop taking all their medications and trials involving genetic testing.

Tran said some potential participants also fear being used as “guinea pigs” – of unpredictable effects on their health. While Frontier usually performs trials of drugs already taken by enough people to “establish that there is no immediate severe effect that we’re aware of,” any side effects reported so far are reported to potential new volunteers, he said.

Participants can quit at any time, he added: “You’re not stuck.”

Webb said bipolar disorder runs in his family. When his trial ends after a year, he plans to ask his primary care doctor to prescribe the drug he credits with helping him now.

While Abilify is often marketed now as an add-on treatment for people already taking another antidepressant, Webb said, in this case an injectable dose of that drug alone seems to be effective against his mental illness.

If it works for other people, too, he said, he’s glad to do what he can to help.

“You talk about Spokane, there’s a lot of people out there who got what I got,” Webb said.


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