University of Alberta to Launch Clinical Trials for Hepatitis C and Long COVID

University of Alberta researchers will lead two new cross-Canada clinical trials to help prevent hepatitis C (HCV) and treat long COVID, thanks to a grant of nearly $5.5 million announced today by the Canadian Institutes of Health Research.

Lawrence Richer, a pediatric neurologist and director of the Northern Alberta Clinical Trials and Research Centre, received $3,266,550 to lead a trial testing the efficacy of taurine supplements to treat long COVID symptoms, based on recent promising research by Gavin Oudit, cardiologist and clinician-scientist at the Mazankowski Alberta Heart Institute, and others.

Infectious diseases specialist Vanessa Meier-Stephenson received $2,178,000 to lead a trial testing the safety and efficacy of a hepatitis C vaccine developed in the laboratory of Michael Houghton, director of the Li Ka Shing Applied Virology Institute and co-winner of the Nobel Prize in Physiology or Medicine.

Targeting inflammation in long COVID

The U of A study team that first identified low taurine levels in the blood as a predictive biomarker and potential treatment target for long COVID has since published another paper suggesting that taurine supplementation has already demonstrated clinical benefits in other diseases and now warrants large-scale clinical trials as a treatment for post-COVID condition. Long COVID, or post-COVID condition, is when symptoms last longer than 12 weeks following infection with the COVID-19 virus.

Taurine is an amino acid produced by the liver and also found in food that supports nerve growth, digestion, muscle function and the immune system. It is a required additive in baby formula and pet food, and is often added to energy drinks. Taurine also has anti-inflammatory properties.

It’s believed inflammation of the blood vessels in the brain is linked to long COVID symptoms such as fatigue and brain fog, although the mechanism is not entirely understood, Richer and Oudit say.

“Those symptoms exist in other patients such as those with multiple sclerosis and undergoing chemotherapy for cancer,” Richer says. “It could be that many diverse causes from various conditions are all leading to the same underlying mechanism.”

He notes that patients report they are more comfortable taking a food supplement that has already been proven safe than a brand-new medication, but he cautions to wait until the evidence is in.

“There are a whole lot of thoughts and ideas about what might be helpful for long COVID but precious little evidence, so this trial is really all about meeting the expectations that patients have — that things that are being recommended to them come with some degree of evidence,” he says.

The trial is considered Phase 2 because it is evaluating an approved supplement for a new use. The team aims to enrol 300 patients in six centres across Canada, at sites including Edmonton’s Long COVID Clinic and the Royal Alexandra Hospital. Patients with long COVID and primary care physicians from the community will join the research team. Trial participants will be randomized to receive either a placebo or a daily taurine supplement for two months and will be followed for six months to monitor their symptoms.

The trial will be carried out under the umbrella of the REcovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine (RECLAIM), a national randomized trial comparing the effectiveness of various interventions for lingering symptoms of COVID-19, and will tap into the expertise of the Long COVID Web, a Canadian network of scientists and patients conducting research into post-COVID condition. Richer is on the operating committee of the Accelerating Clinical Trials (ACT) Canada Consortium, a $39-million plan to expand clinical trial research in Canada. He is also associate dean of health research for the College of Health Sciences at the U of A and a member of the Women and Children’s Health Research Institute.

Preventing HCV infection

Houghton’s Nobel Prize was jointly received along with Harvey Alter and Charles Rice in recognition of their discovery of the hepatitis C virus and the subsequent development of a test for HCV that has saved millions of lives. He has since devoted his career to developing a vaccine to prevent infection with the virus.

Hepatitis C is a blood-borne virus that affects the liver, causing either acute or chronic hepatitis that can lead to liver disease, liver cancer or death. It’s most commonly transmitted through unsafe injections, non-sterile medical equipment, anal sex, or transfusion of contaminated blood. Chronic hepatitis C virus affects 58 million people worldwide, including more than 250,000 in Canada, where rates of new diagnosis are 2.5 times higher among First Nations people than the general population. The World Health Organization has set the ambitious goal to eradicate HCV infection by 2030 through both treatment and vaccination.

The new vaccine to be tested is a second-generation combination approach developed by Houghton and his team. The first component, which has been the subject of an encouraging clinical trial on its own, acts on the B cells in the recipient’s body, causing them to make antibodies that bind to the pathogen and neutralize it. The second component employs a new approach to activating T cells that directly attack pathogens and help the immune system recognize and respond to threats. The third component is called an adjuvant, which heightens the action of the other two ingredients.

Meier-Stephenson says the goal is to prevent primary infections, reinfections and the chronic illness that often follows infection. The vaccine was designed based on the most common genotype, which causes 40 per cent of cases, but early data shows potential for cross-coverage of all seven genotypes.

“This combination could be a game-changer for HCV eradication and have great benefits for patients not just in Canada but worldwide,” she says. “There are medications for hepatitis C available but they are expensive and not readily available in some countries, so the vaccine has the potential to have a broader reach.”

Five to 10 healthy volunteers will be enrolled at first to test the safety of the vaccine, then about 60 more will be randomized to receive either the control placebo or the vaccine at different doses to test its efficacy at sign-up, one month and six months. Patients will be recruited in Edmonton, Ottawa and Toronto. Their response to the vaccine will be monitored by analyzing blood work for their immune response. If the vaccine proves effective, the next steps would be Phase 2 and Phase 3 trials of efficacy that would involve challenging healthy individuals with exposure to the virus after vaccination, and if not protected, curing them of the virus with known drugs. The current trial does not involve any infection, just the vaccine.

Meier-Stephenson, who also leads the clinical trial for a new streptococcus A vaccine launched two years ago, says the priority at all phases will be the safety of the volunteer participants.

“These types of studies are necessary to prove safety and efficacy of new products, but there’s a high level of scrutiny,” she says. “These are healthy people and we — our trial physicians — have all taken the oath to do no harm, so any signal will be followed up carefully.”

The funding is part of Canada’s Biomanufacturing and Life Sciences Strategy, which also recently awarded nearly $100 million to U of A for pandemic preparedness projects.