Coma & Chronic Disorders of Consciousness Coordinating Panel on Rare Neurological Diseases

Treating Disorders of Consciousness With Apomorphine: a Clinical Trial Using Multimodal Assessments

Three patients with chronic disorders of consciousness showed behavioural and neuroimaging improvements after 30 days of treatment by apomorphine in the pilot phase of a multimodal clinical trial launched in Liège, Belgium.

Treatment with apomorphine, a dopamine agonist, has exhibited promising effects to improve recovery from coma. We report the launch of a multicentre study using multimodal assessments to confirm its efficacy and investigate its action on brain activity in patients with disorders of consciousness (DOC), led by the Coma Science Group in Belgium.

This prospective double-blind parallel randomized placebo-controlled trial will include 48 patients with DOC, who will receive a 30-day regimen of either apomorphine or placebo subcutaneous infusions. They will be monitored 30 days before therapy, during treatment and 30 days after washout, using standardized behavioral scales, neurophysiological measures and brain imaging. See [1] for the detailed protocol.

A preceding open-label pilot phase following the same protocol was started to provide operational experience, interim data and evaluate feasibility. Preliminary results on the first three treated patients show multimodal improvements after treatment. All three patients exhibited new and/or more frequent conscious behaviors after the initiation of apomorphine, leading to durable changes of clinical diagnosis for two of them. Additionally, brain metabolism measured by FDG-PET increased in all patients, while EEG functional connectivity and multivariate classification improved for two patients and remained stable for the third.

As the contribution of spontaneous recovery to these improvements cannot be appraised at this stage, the randomized controlled phase will be necessary to confirm the efficacy of apomorphine treatment for the recovery of consciousness. These promising results illustrate the high potential impact of apomorphine on the management of these patients in urgent need for better healthcare.

 

 

Key points

  • Apomorphine is a dopamine agonist that may be a promising candidate for the treatment of chronic disorders of consciousness.
  • Its true efficacy and its action on brain activity need to be investigated in controlled conditions with a large patient sample.
  • A multicentre double-blind parallel randomized placebo-controlled clinical trial will be conducted at the University of Liège to assess the effects of apomorphine for the recovery of consciousness
  • Preliminary results of the open-label pilot phase show behavioural and neuroimaging improvements after apomorphine treatment in all treated patients.
  • Further data and proper placebo control will allow to confirm the efficacy of this promising therapeutic candidate.

 

References

 

[1] Sanz, L. R. D., Lejeune, N., Blandiaux, S., Bonin, E., Thibaut, A., Stender, J., et al. (2019). Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments. Front. Neurol. 10, 1–10.
doi:10.3389/fneur.2019.00248.

[2] Sanz, L. R. D., Lejeune, N., Blandiaux, S., Bonin, E., Raimondo, F., Panda R., et al. (2019). Clinical and neuroimaging improvements after apomorphine treatment in a patient with chronic disorders of consciousness following brain hemorrhage. Oral and poster communications at the 13th World Congress on Brain Injury, Toronto, March 2019, Brain Inj.