Exenatide Trials: My Story

I got involved in trials back in 2013 when a friend of mine saw a leaflet asking for volunteers at her GP practice.

Phase 1 was a not blinded proof- of-concept and I ended up in the control group that didn’t take the active drug. This allowed me to be part of the double-blinded phase 2 trial in 2014/15, where volunteers were randomised into injecting Exanatide or a placebo once a week over the course of a year. I did feel a bit nervous at first, this being my first delve into the world of research, but the research team put me at ease quickly. And with Exanatide already being tested & approved for diabetes, the risks were minimal.

The trial required me to inject myself once a week into either thigh or belly, and once you get over sticking a needle into yourself, that’s fine. Every 3 months I travel to the UCL in London for a half day assessment. This required me to stop my usual Parkinson’s medication for 24 hours to allow the research team to see me both in off and on state. They conducted a series of test checking motor functions and cognitive abilities. I also had regular blood and urine tests as well as a DAT scan and spinal fluid test at the start and finish of the trial period.

Overall a very positive experience, it was great having an extra few pairs of hands and eyes taking care of me for a couple of years.

See also this video of Dr. Dilan Athauda explaining the background and history of how Exanatide came into play for Parkinson’s. At the very end Dilan ventures further into the brave new world of drug repurposing, i.e. using medication already tested and approved for other illnesses, e.g. diabetes for use in treatment of other diseases such as Parkinson’s. International experts have compiled a list of 7 promising candidates and I’ve been lucky enough to be involved in trials for 2 of these (Exanatide & Simvastatin).

Just wanted to give an update on my personal journey as Exanatide is currently moving into a third trial phase, involving more participants over a longer period of time.

About a year after phase 2 trial ended back in 2016, the results were very promising, indicating that patients with the active drug showed significant improvement in motor symptoms over the trial period and also at the checkpoint 2 month after trial end, compared to the placebo control group. As it turned out, I had been on the active drug and my test results were in line with the overall assessment showing improvement beyond trial end.

When it came to discussing next steps in my personal journey with Parkinson’s and managing my symptoms with the right cocktail of medication, it was decided by my neurologist and GP that I would benefit from receiving Exanatide on an ongoing basis. I’m having quarterly blood tests to check for any unwanted side effects, but so far so good. When I think about this, I’m probably one of only a handful of PwP who are taking this leading-edge medication to fight their disease – and that is quite a humbling thought.

© Ulli Funken 2019, 2021

Exenatide Phase 2
Editor’s Notes: Summary of Trial Results © The Lancet

Clinical Trial identifier http://clinicaltrials.gov/show/NCT0197242

Background
Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson’s disease. We investigated whether these effects would be apparent in a clinical trial.

Methods
In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson’s disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25–75 years, had idiopathic Parkinson’s disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed.

Findings
Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI −2·6 to 0·7) in the exenatide group and worsened by 2·1 points (−0·6 to 4·8) in the placebo group, an adjusted mean difference of −3·5 points (−6·7 to −0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions.

Interpretation
Exenatide had positive effects on practically defined off-medication motor scores in Parkinson’s disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.

Funding
Michael J Fox Foundation for Parkinson’s Research.