Waban, Massachusetts, and Liège, Belgium (Dec 05, 2018) – NeuroHealing
Pharmaceuticals and the Coma Science Group at the GIGA-Consciousness,
University of Liege announce the treatment of the first patient in the
clinical trial: “Treating severe brain-injured patients with
apomorphine: a behavioral and neuroimaging study.

The study (ClinicalTrials.gov Identifier: NCT03623828, EudraCT
Identifier 2018-003144-23) will investigate the effects of
subcutaneously administered apomorphine in brain-injured patients with
disorders of consciousness. The study is designed to confirm
previously observed positive clinical responses in these patients and
to correlate behavioral improvements with multimodal neuroimaging
techniques.  Results should help to define clearer guidelines in the
treatment of patients with disorders of consciousness and allow a
better understanding of how dopamine networks are involved in
consciousness and its impairments.

The study is being conducted at the Coma Science Group and the William
Lennox Neurological Hospital Center, Belgium. The Coma Science Group
is one of the leading research centers in the world for the study of
patients with altered states of consciousness. It aims to improve the
medical care of patients in a coma, unresponsive wakefulness syndrome
and minimally conscious states, as well as investigate the neural
correlates of consciousness. William Lennox Neurological Hospital
Center is a renowned hospital and an expertise center for the
neurological rehabilitation of patients with disorders of

Principal Investigator is Steven Laureys, M.D., PhD, Clinical
Professor and Head of the Coma Science Group at the GIGA Institute of
Liège, and Research Director at the Belgian National Fund for
Scientific Research (www.coma.ulg.ac.be/home/steven.html). He is
recognized worldwide as a leading clinician and researcher in the
field of neurology of consciousness.  He has over 450 papers in the
field and has published several books including The Neurology of
Consciousness (with G. Tononi, 2008, 2015); Coma Science (with A. Owen
and N. Schiff; 2009) and Disorders of Consciousness (with N. Schiff,
2009).Key members of the Belgium study research team include Study Chair
Olivia Gosseries, PhD, Leandro Sanz, M.D., Nicolas Lejeune, M.D.,
Estelle Bonin, MSc, Séverine Blandiaux, MSc, and Aurore Thibaut, PhD.

“We are very excited to start this clinical trial which will assess in
a controlled setting the efficacy of this promising drug for the
treatment of this very challenging patient population. We currently
have very limited therapeutic options to help patients recovering from
coma and apomorphine could be a game-changer” says Steven Laureys, PI.

Study Design

Previous studies (Fridman, et al 2009, 2010) have shown that
apomorphine, a direct non-specific dopaminergic agonist, can
dramatically improve the outcome of patients with disorders of
consciousness within days to weeks of treatment. Notably, these
patients had been previously treated with other dopaminergic agents,
without response.

This study will investigate the response to a 30-day treatment regimen
of daily subcutaneous infusions of apomorphine in patients with an
unresponsive wakefulness syndrome or in a minimally conscious state.
In an initial study phase, the treatment will be known by the
physician and patient’s family (open-label), before a second phase
with a placebo-controlled double-blind randomized design.

Outcome measures will include standardized behavioral assessments
along with advanced multimodal brain imaging techniques, combining
magnetic resonance imaging (MRI), positron emission tomography (PET),
electroencephalography (EEG), actigraphy and core body temperature
monitoring data. These techniques may help to identify a set of
biomarkers that correlate with responsiveness to the therapy and
pinpoint the neural networks targeted by dopamine agonists in these

Patients will be monitored at baseline 30 days before initiation of
therapy, during treatment and for 30 days after treatment washout.
Long-term behavioral follow-up will be performed up to 2 years using
structured phone interviews. Statistical analyses will be performed
blindly to detect changes in behavioral status, circadian rhythmicity,
brain metabolism and functional connectivity both at the individual
and at the group level.

Further details are provided in Sanz et al., (2018) “Treating severely
brain-injured patients with apomorphine: study protocol for a double
blind randomized placebo-controlled trial using behavioral and
neuroimaging assessments.”

This clinical trial will be discussed along with currently available
treatments and future therapeutic options during the “Coma Day” event
in Liège on December 12, 2018.

About GIGA ConsciousnessThe Coma Science Group at the GIGA-Consciousness aims to better
understand and explain the origins of human consciousness by studying
pathological, pharmacological and physiological modifications of
conscious awareness in both patients and healthy subjects. Expertise
ranges from the assessment of brain function in (i) brain death, coma,
unresponsive wakefulness syndrome, minimally conscious state and
locked-in syndrome patients to (ii) general anesthesia, controlled
sedation and hallucinatory drugs, to (iii) hypnosis, meditation,
near-death experiences and dream-like states.

Contacts for Further Information

Olivia Gosseries, PhD & Leandro Sanz, MD

GIGA-Consciousness and Coma Science Group

University of Liège and University Hospital of Liège, Belgium



Nicolas Lejeune, MD

GIGA Consciousness and Coma Science Group

Institute of NeuroScience, UCLouvain

Centre Hospitalier Neurologique William Lennox, Groupe Hospitalier
Saint-Luc, Ottignies, Belgium



Neal M. Farber, PhD

NeuroHealing Pharmaceuticals, Inc.


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