New Zealand scientists are leading some of the most fascinating clinical trials in the world – yet few Kiwis are likely aware of them. Science reporter Jamie Morton looks at five exciting programmes awarded funding
from the Health Research Council.

Kōwhai chemical could help smokers quit

It’s found in a number of Aotearoa’s native plants, including our colourful kōwhai – and it could well help the country’s bid to soon be smokefree.

That’s cytisine, a plant extract that’s been used for decades in smoking cessation treatment in some Central and Eastern European countries, and more recently in Canada, but remains relatively unknown elsewhere in the world.

Like varenicline, a Government-funded smoking medication marketed as Champix, cytisine works by reducing the feeling of satisfaction that smoking gives – and stops the unpleasant feelings that come after stopping.

Yet it’s also cheaper than Champix and other medications, has few known side effects and is more effective than nicotine replacement therapy at helping people to quit smoking.

“We have also shown in a trial that cytisine is at least as effective and more acceptable to Māori and whānau of Māori who smoke and are trying to quit, than Champix – plus cytisine has fewer side-effects,” University of Auckland researcher Associate Professor Natalie Walker said.

“Our research has also shown that text-messages offering advice and support around quitting smoking are highly effective and acceptable.”

In an upcoming trial, also funded by the Health Research Council of New Zealand, Walker and her team want to take all they’ve learned about cytisine’s benefits – and test it against other “best of the best” smoking cessation products.

“Individually, there is nothing better than cytisine, nicotine e-cigarettes or text messaging to help you quit smoking – so what happens when you put them all together?”

Among a pool of 800 participants – with almost 100 already recruited – the team aim to trial cytisine alone, nicotine e-cigarettes alone or both products in combination with supportive text messages.

It will also be one of the world’s first trials to test the effectiveness of new nicotine salt pod e-cigarettes.

• People interested in learning more about the study can visit the website.

Is this infertility treatment unfairly shunned?

For the thousands of Kiwi couples who experience it, unexplained infertility often comes with years of heartbreaking uncertainty and costly procedures.

While most of these couples choose in vitro fertilisation, or IVF, one group of researchers want to test whether that really is a better clinical path than the other publicly-funded treatment available, intrauterine insemination, or IUI.

What’s the difference?

In IUI, fertilisation takes place through the sperm being directly injected into the uterus, where an embryo implants itself if the treatment succeeds.

With IVF, the sperm and egg are combined for fertilisation in a lab, before one or more fertilised eggs are placed into the uterus.

“Although the New Zealand funding model offers eligible couples with unexplained infertility a choice between IUI and IVF, couples overwhelming select IVF, even though it has a one-year waiting list, and there’s no waiting list for IUI,” said Professor Cindy Farquhar, of the University of Auckland.

She and colleagues speculated couples and clinicians more often opted for IVF because they considered it superior in terms of live birth rate, time to pregnancy, and the possibility of creating surplus embryos.

On the other hand, IUI was less invasive, and also cheaper: one round of IVF was about the same cost as three or four IUI cycles.

Farquhar, one of New Zealand’s leading academics in fertility and womens’ health, said the three major studies carried out to date had found three to six cycles of IUI were comparable to IVF.

The majority of IUI procedures in those studies used a technique called gonadotrophin ovarian stimulation – which in some cases led to high rates of multiple pregnancies.

But taking a different approach to ovarian stimulation – and using a medication called clomiphene citrate – was known to result in lower multiple pregnancy rates.

A 2017 study led by Farquhar also found that using IUI with clomiphene was three times more effective than continuing to try to get pregnant without treatment.

“These findings suggest that IUI ovarian stimulation (IUI-OS) is a successful and cost-effective fertility treatment for this population, in which IVF usually offers a live birth rate of a similar magnitude.”

Through an ongoing programme called The FIIX Study, Farquhar’s team aim to answer some of the biggest questions surrounding the two interventions’ comparative success for couples with unexplained infertility.

Compared with one complete round of IVF, did four cycles of IUI-OS really deliver a poorer result for cumulative live births – and did the cost per live birth come in lower?

Or would four cycles of IUI-OS followed by two complete rounds of IVF result in more births, and at a cheaper cost per birth, than using IVF alone?

Farquhar said 467 participants identified from the IVF public funding waitlist have already been recruited for the study, which was expected to be one of the largest of its kind.

If it indeed showed IUI-OS wasn’t inferior to IVF, the benefits for the country’s fertility funding model could be far-reaching – and enable couples faster access to treatment.

Smarter caries treatment could ease kids’ dentophobia

We all remember that childhood fear of visiting the dental clinic.

Unfortunately for many of us, Dr Joanne Choi said, that dentophobia early in our lives may have had lasting consequences for the health of our teeth.

“Having dental anxiety can set up a child for lifelong dental problems – they may avoid going to the dentists while they grow up, affecting their oral health and quality of life,” said Choi, of Otago University’s Faculty of Dentistry.

Much of it likely owed to the drilling and injections that came with treatment for dental caries – a common childhood disease estimated to affect 530 million kids here and around the world.

For decades, dental caries have been treated with the “drill and fill” method, or injection with resin or amalgam fillings.

However, these materials had a limited lifetime – and often left children having to go through this painful procedure numerous times.

An alternative approach was a no-drill, no-injection procedure called the Hall Technique.

Instead of drilling the affected tooth, it used preformed metal crowns, or PFCs, which were capped over the tooth to seal off the risk of decay.

Although effective clinically, Choi said this technique came with a certain “aesthetic limitation” that being the crown was silver, rather than the natural colour of teeth.

“The metal PFCs also have other disadvantages: cost to healthcare providers is high and placement can be difficult.”

Having developed and validated a novel white cap crown system for the Hall Technique, Choi and her team are now preparing for a clinical trial to be carried out across the country.

Before that could happen, however, the team had to test the therapeutic feasibility of the new crowns.

One challenge they’d already encountered was to work out how to adapt the crowns to the teeth of Māori and Pasifika children, which didn’t fit so well with European-centric PFCs.

After digitally scanning the teeth of some 200 kids of different ethnicities, the researchers will soon be finalising their designs for the crowns that’ll ultimately be used in the feasibility clinical trial.

“To our knowledge, we are the first one to conduct any clinical trial with white crowns for the Hall Technique,” Choi said, adding that their work could potentially go on to transform the international dental market.

Does giving babies paracetamol cause asthma later?

Does giving babies paracetamol put them at higher risk of developing asthma later in life?

That’s what a team of Kiwi scientists have been trying to answer in a world-first, multi-million dollar study that’s been running since 2017, known as the PIPPA Tamariki study.

So far, Professor Stuart Dalziel and his colleagues have delivered some reassuring findings – that both paracetamol and ibuprofen, which paracetamol is being compared against among more than 3200 children in their programme, were both extremely safe, with few short-term side effects.

But Dalziel said more time and more study participants, the team are aiming for 3922, were needed to see if paracetamol in the first year of life didn’t present an asthma risk.

One major study, which drew on data from 200,000 children in 31 countries, suggested that risk may exist.

Yet it was unclear whether asthma resulted from the use of paracetamol itself, or merely illnesses, like viral infections, that the drug was used to treat.

In any case, Dalziel, Cure Kids Chair of Child Health Research at the University of Auckland and a paediatric emergency medicine specialist at Starship Children’s Hospital, saw an urgent need to find ways to reduce the prevalence of asthma in kids.

New Zealand’s child asthma rates remain stubbornly among the highest in the world, with one in seven children and one in nine adults receiving treatment for it.

“What we’ve done in the short-term is prove that [paracetamol and ibuprofen] are incredibly safe,” Dalziel said.

“What we don’t have yet is long-term data, as no one has ever done a study like this.”

The team aimed to complete enrolment of the study’s next intake – involving 700 more children – by mid-2023, and then follow that cohort for another six years.

Along with asthma, Dalziel said the study would provide “incredibly useful” data on the two medications and asthma, along with eczema, bronchiolitis and other respiratory conditions.

• Families with newborn babies younger than eight weeks old who wish to join this study can contact the team at www.pippatamariki.ac.nz.

Could LSD ‘micro-dosing’ treat depression?

We’re much more likely to think of LSD as a mind-bending psychedelic drug than a pharmaceutical treatment.

But, when taken in extremely small doses, scientists suspect lysergic acid diethylamide, along with psilocybin, could play a useful role as an alternative therapy – specifically for depressive disorders.

Around the world, sufferers of depression have increasingly been turning to “micro-dosing” – that’s typically taking five or 10 per cent of a full dose of a psychedelic hallucinogen – as self-treatment.

Beyond anecdotal reports, however, the effect is unclear: and there have been no randomised controlled trials to support the practice.

That’s where the University of Auckland’s Associate Professor Dr Suresh Muthukumaraswamy and his team want to shed more light.

Having completed a phase one study with 80 healthy volunteer participants, the team is moving to find if eight weeks of LSD microdosing – compared with a placebo – brings a big reduction in symptoms in patients with major depressive disorder.

“Globally, an estimated 260 million people suffer from depression with new treatments clearly needed to help reduce the health and economic burden of depression for these individuals, their whānau and communities,” Muthukumaraswamy said.

“If promising results are found in this trial, then further pharmaceutical trials could be developed in collaboration with the nascent psychedelic pharmaceutical industry.”

Given the generic nature of psychedelics such as LSD and psilocybin, they were likely to be inexpensive therapies, he said.

“Alternatively, if microdosing is found to be ineffective, then the many thousands of depressed patients self-medicating with microdosed psychedelics worldwide can be encouraged to return to evidence-based care.”

New Zealand wasn’t the only country investigating potential benefits of LSD microdosing – but it was well placed to deliver some of the earliest results.

“Indeed, there are a couple of trials world-wide – I think they are all at the stage we are at – in the set-up phase and not yet commenced,” he said.

“So, there is a bit of ‘competition’ but that’s good – more data will speak to whether this intervention that can really work. It also speaks to the promise of the work.”

• Patients interested in taking part can register here.