University of Alberta Hospital is one of 50 international research centres worldwide and one of only five in Canada that have been selected to participate in a Phase II clinical trial of a promising new compound being developed as a potential treatment for Attenuated Positive Psychotic Symptoms (APSS).
The condition, which manifests as very mild symptoms of psychosis among affected adolescents and young adults, is regarded as a prodrome - or a potential advance indicator - of schizophrenia. Currently, there are no approved treatments for those who exhibit early symptoms of psychosis.
Global pharmaceutical giant Boehringer Ingelheim is developing the drug, known simply as BI 409306. Local participant screening and recruitment for the trial is slated to begin in mid-May.
"As clinicians we have no medications now for treating APSS and we are quite hesitant to use anti-psychotics on teenagers and young adults because these are very potent drugs," says Dr. Pierre Chue, Clinical Department Head for Addiction and Mental Health, Edmonton Zone, with Alberta Health Services.
"If this drug (BI 409306) is successful, it could be a game-changer in the same way that Prozac was a game-changer for depression. You would have the potential of a safe and effective medication that could potentially transform peoples' lives by preventing transition into psychosis."
Chue, a Clinical Professor in the University of Alberta's Department of Psychiatry, is the trial's Principal Investigator at UAH. Dr. Adam Abba-Aji, local Medical Director for the national young adult mental health program, ACCESS Open Minds, and a fellow Faculty member of Chue's in the Department of Psychiatry, is the Sub Investigator.
The University of Calgary's Department of Psychiatry is also participating at a second trial site in Calgary.
Scott Jamieson, Director of Clinical Operations, Clinical Research Unit Edmonton (CRUE), and Karen Martins, CRUE's Clinical Operations Project Lead and Clinical Coordinator for the trial, are providing related trial support services.
CRUE - a joint effort between the University of Alberta's Quality Management in Clinical Research Department (QMCR) and the Northern Alberta Clinical Trials & Research Centre (NACTRC) - coordinates patient recruitment, regulatory affairs, clinical trial monitoring, data safety monitoring and budgeting on an as-needed, a la carte basis.
"This clinical trial is unique in many respects. It's the first study that the Clinical Trials & Research Program is about to embark on at the University of Alberta, and it will also be looking at a target population that has not had any opportunity for treatments before, and with a novel compound," says Chue.
"We're focusing on individuals who exhibit very early symptoms of psychosis, but they're not severe enough to make a diagnosis, and not necessarily clearly indicative of schizophrenia at that point. These are things like increased social difficulty, falling academic performance, disrupted sleep and problems with thinking, or other subtle signs that something is amiss. Typically this occurs over a one to two-year period before any full-blown psychotic symptoms emerge."
Developing an effective medication for early intervention and treatment of the target population is a key goal of clinicians. At least fifty per cent of those who exhibit symptoms of an early psychosis will develop schizophrenia.
"Up until now this group has gone under-recognized and under-treated, and as a consequence we often only see individuals once they've dropped out of high school or university or wind up living on the street. They may only be in their 20s but by then the illness has already been present and untreated for four or five years," Chue explains.
"If we can intervene within the first two years of the illness or earlier, we can have a very positive impact on both the individuals affected and society as a whole. These individuals could probably finish school, go to university, get a job and have a family, as opposed to suffering a very negative and potentially deteriorating course."
The focus on early intervention and treatment is consistent with various public policy initiatives that have also targeted children and adolescents, including Valuing Mental Health, a 2015 report by the province's Alberta Mental Health Review Committee; Valuing Mental Health - Next Steps, a follow-up report released in mid-2017; and Alberta Health Services' Patient First Strategy.
Although Boehringer Ingelheim's compound is aimed at treating APSS, it is not a conventional anti-psychotic drug, says Chue. Instead, BI 409306 blocks the action of a specific enzyme, phosphodiesterase-9, thereby improving cognition and potentially normalizing dysfunctional brain development in those with the syndrome.
"At the moment all we have are drugs that reduce the delusions and hallucinations of schizophrenia by reducing a chemical called dopamine in the brain. But that typically represents a later stage and by that time the brain pathways are already irreversibly altered. So we're using medications to control the symptoms, but we're not doing anything to affect the causes of the illness."
Chue and his colleagues are currently gearing up to launch the patient recruitment process for the trial, which becomes active at the UAH site on May 16th. They are considering using social media to reach out to students at the University of Alberta who might be interested in participating. They may also contact counsellors at Edmonton-area schools so they can inform students and families about the trial. Public advertising is another option under consideration.
"Since the goal is to identify individuals at the very early stages of the illness, we probably won't be recruiting from our outpatient programs or clinics. If individuals have reached that point then most likely they already have the illness and wouldn't be appropriate candidates for this study."
Those who are simultaneously dealing with substance abuse issues would also be ruled out as viable candidates. As a result, although the goal is to recruit just five patients at the UAH trial site, Chue and Martins agree that many times that number of potential candidates will have to be screened upfront before five suitable participants are identified.
Once they are recruited, patients who receive the drug will be treated for a one-year period. Results from the Phase II trial are not expected to be released until at least 2021.
Another key component of the trial is that it is a joint effort involving both the U of C in Calgary and the U of A, says Chue.
"This is one of the first examples of a reciprocal ethics arrangement for both locations. Previously, you'd have to get separate approvals at the U of C and the U of A, with additional costs and time. Now it's a very simplified approval. This is an example of increased cooperation and collaboration between the two universities as well as the support from NACTRC and CRUE, which has really streamlined the whole clinical trial process for us."
The condition, which manifests as very mild symptoms of psychosis among affected adolescents and young adults, is regarded as a prodrome - or a potential advance indicator - of schizophrenia. Currently, there are no approved treatments for those who exhibit early symptoms of psychosis.
Global pharmaceutical giant Boehringer Ingelheim is developing the drug, known simply as BI 409306. Local participant screening and recruitment for the trial is slated to begin in mid-May.
"As clinicians we have no medications now for treating APSS and we are quite hesitant to use anti-psychotics on teenagers and young adults because these are very potent drugs," says Dr. Pierre Chue, Clinical Department Head for Addiction and Mental Health, Edmonton Zone, with Alberta Health Services.
"If this drug (BI 409306) is successful, it could be a game-changer in the same way that Prozac was a game-changer for depression. You would have the potential of a safe and effective medication that could potentially transform peoples' lives by preventing transition into psychosis."
Chue, a Clinical Professor in the University of Alberta's Department of Psychiatry, is the trial's Principal Investigator at UAH. Dr. Adam Abba-Aji, local Medical Director for the national young adult mental health program, ACCESS Open Minds, and a fellow Faculty member of Chue's in the Department of Psychiatry, is the Sub Investigator.
The University of Calgary's Department of Psychiatry is also participating at a second trial site in Calgary.
Scott Jamieson, Director of Clinical Operations, Clinical Research Unit Edmonton (CRUE), and Karen Martins, CRUE's Clinical Operations Project Lead and Clinical Coordinator for the trial, are providing related trial support services.
CRUE - a joint effort between the University of Alberta's Quality Management in Clinical Research Department (QMCR) and the Northern Alberta Clinical Trials & Research Centre (NACTRC) - coordinates patient recruitment, regulatory affairs, clinical trial monitoring, data safety monitoring and budgeting on an as-needed, a la carte basis.
"This clinical trial is unique in many respects. It's the first study that the Clinical Trials & Research Program is about to embark on at the University of Alberta, and it will also be looking at a target population that has not had any opportunity for treatments before, and with a novel compound," says Chue.
"We're focusing on individuals who exhibit very early symptoms of psychosis, but they're not severe enough to make a diagnosis, and not necessarily clearly indicative of schizophrenia at that point. These are things like increased social difficulty, falling academic performance, disrupted sleep and problems with thinking, or other subtle signs that something is amiss. Typically this occurs over a one to two-year period before any full-blown psychotic symptoms emerge."
Developing an effective medication for early intervention and treatment of the target population is a key goal of clinicians. At least fifty per cent of those who exhibit symptoms of an early psychosis will develop schizophrenia.
"Up until now this group has gone under-recognized and under-treated, and as a consequence we often only see individuals once they've dropped out of high school or university or wind up living on the street. They may only be in their 20s but by then the illness has already been present and untreated for four or five years," Chue explains.
"If we can intervene within the first two years of the illness or earlier, we can have a very positive impact on both the individuals affected and society as a whole. These individuals could probably finish school, go to university, get a job and have a family, as opposed to suffering a very negative and potentially deteriorating course."
The focus on early intervention and treatment is consistent with various public policy initiatives that have also targeted children and adolescents, including Valuing Mental Health, a 2015 report by the province's Alberta Mental Health Review Committee; Valuing Mental Health - Next Steps, a follow-up report released in mid-2017; and Alberta Health Services' Patient First Strategy.
Although Boehringer Ingelheim's compound is aimed at treating APSS, it is not a conventional anti-psychotic drug, says Chue. Instead, BI 409306 blocks the action of a specific enzyme, phosphodiesterase-9, thereby improving cognition and potentially normalizing dysfunctional brain development in those with the syndrome.
"At the moment all we have are drugs that reduce the delusions and hallucinations of schizophrenia by reducing a chemical called dopamine in the brain. But that typically represents a later stage and by that time the brain pathways are already irreversibly altered. So we're using medications to control the symptoms, but we're not doing anything to affect the causes of the illness."
Chue and his colleagues are currently gearing up to launch the patient recruitment process for the trial, which becomes active at the UAH site on May 16th. They are considering using social media to reach out to students at the University of Alberta who might be interested in participating. They may also contact counsellors at Edmonton-area schools so they can inform students and families about the trial. Public advertising is another option under consideration.
"Since the goal is to identify individuals at the very early stages of the illness, we probably won't be recruiting from our outpatient programs or clinics. If individuals have reached that point then most likely they already have the illness and wouldn't be appropriate candidates for this study."
Those who are simultaneously dealing with substance abuse issues would also be ruled out as viable candidates. As a result, although the goal is to recruit just five patients at the UAH trial site, Chue and Martins agree that many times that number of potential candidates will have to be screened upfront before five suitable participants are identified.
Once they are recruited, patients who receive the drug will be treated for a one-year period. Results from the Phase II trial are not expected to be released until at least 2021.
Another key component of the trial is that it is a joint effort involving both the U of C in Calgary and the U of A, says Chue.
"This is one of the first examples of a reciprocal ethics arrangement for both locations. Previously, you'd have to get separate approvals at the U of C and the U of A, with additional costs and time. Now it's a very simplified approval. This is an example of increased cooperation and collaboration between the two universities as well as the support from NACTRC and CRUE, which has really streamlined the whole clinical trial process for us."