GRANTS. Two Gothenburg-based applicants receive multi-million kronor sums from the Swedish Research Council’s call for clinical treatment research. Bo Söderpalm is receiving SEK 17 million for a collaborative project that can result in more effective pharmacological treatment for people with alcohol dependence, and Anders Jeppsson is receiving fully SEK 7.5 million for another national project, which will study which of two different treatments works best for the prevention of complications after coronary artery bypass surgery.
In total, the Swedish Research Council is funding 18 projects in a research environment in clinical treatment research with a total of nearly SEK 230 million. All projects are conducted as national multi-centre studies, and the University of Gothenburg is the administrating organisation for two of them.
More effective treatment of alcohol dependence
The project that Bosse Söderpalm will lead involves researchers in Gothenburg, Linköping, Malmö/Lund and Stockholm, and is now receiving SEK 17 million from the Swedish Research Council in order to be carried out. In the clinical multi-centre study, 320 patients with alcohol dependence will be selected and randomized to either receive a combination treatment with both varenicline and bupropion hydrochloride, to receive one of these active substances combined with a placebo, or to receive two placebo pills – that is, no treatment whatsoever. For the study, the treatment will be given for three months and its effects will be measured using the biomarker B-PEth, which has been shown to be highly reliable for measuring regular intake of alcohol, including in studies here in Gothenburg.
Today’s medications to treat alcohol dependence have a limited effect: only one in eight, or even one in ten patients respond to the treatment. Bosse and his colleagues are optimistic that this study can lead to a treatment with significantly improved effects.
“We have previously conducted a clinical study in which we treated people with alcohol dependence with varenicline, which is one of the most effective medications for smoking cessation. We observed a slightly improved effect, which American researchers have also been able to show. Based on studies in animal models, we have good reasons to believe that the treatment could be even better if we combine this medication with another substance that is also used for smoking cessation, bupropion”, says Bo Söderpalm.
He can very well imagine that the effect size of the treatment could rise from today’s 0.2 to 0.6: “We believe we will see a solid improvement, and that the treatment may reach effects that we as psychiatrists are used to seeing when giving patients medications for other neuropsychiatric illnesses.”
Strong research base
There is a long research history in Gothenburg on alcohol dependence, the reward system, dopamine levels and nicotine receptors. For 25 years, researchers have been interested in alcohol’s activation of the dopamine system. Among other things, through animal testing, they have been able to show that alcohol uses a certain type of nicotinic receptor to activate the dopamine system, and if this happens for a long period, the entire dopamine system can be put out of play.
“If you abuse addictive substances for a long time, the brain responds by downregulating the dopamine system. We believe that dopamine levels fall, while the ability of the receptors to receive signals from dopamine are impaired. This causes you to lose your motivation and life can feel meaningless without the drug. When the system has been downregulated, we believe it must be raised back up carefully in order for the individual to be able to function normally,” says Bo Söderpalm.
Numerous basic studies show that alcohol and smoking have very similar effects on the dopamine system. The two smoking cessation medications that will be combined in the study are thought to affect the dopamine system in two different, complementary ways. One substance increases the release of dopamine somewhat, while the other prevents the dopamine from disappearing as quickly upon its release, which increases the amount in the brain’s synapses.
Best method for preventing complications after coronary surgery
Anders Jeppsson, professor of cardiothoracic surgery, is leading the other multi-centre project in which the University of Gothenburg is the administrating organisation. The project is receiving a total of fully SEK 7.5 million this year and next, which is a precondition for its implementation.
The study is about how to best prevent blood clotting in patients who have had open coronary artery bypass surgery. It compares so-called dual antiplatelet therapy, where the patient receives both the medications ticagrelor and aspirin, with the most common platelet inhibition treatment after coronary surgery, which is aspirin alone.
It is a large national randomised study in which 2,200 patients undergoing coronary artery bypass surgery are randomly selected to receive single or dual platelet inhibition. In the worst case, events caused by blood clotting can lead to patient death.
“Patients who undergo open surgery are the sickest coronary artery disease patients with the highest risk of recurrence. It is still unclear which treatment is most effective for the prevention of thrombotic events, that is, what we commonly refer to as blood clotting. It has been suggested that dual platelet inhibition is more effective than aspirin alone, but there have been no randomised studies or conclusive data. Dual platelet inhibition can also increase the risk of hemorrhagic complications, hence it is important to compare the two treatment strategies,” says Anders Jeppsson.
In the study, the number of new thrombotic events (death, stroke, heart attack, or new revascularization) and hemorrhagic complications will be compared between the groups 12, 24, 36, 48 and 60 months after the patients treatment with single or double platelet inhibition in conjunction with coronary artery bypass surgery has started.
“Today, only about 25 percent of patients in Sweden receive dual antiplatelet therapy, which is probably due to the fact that there is no evidence for the treatment being more effective, and due to bleeding concerns. More knowledge about which treatment is the safest and most effective after surgery will ultimately result in reduced risk of complications,” says Anders Jeppsson.
TEXT: ELIN LINDSTRÖM CLAESSEN