Clinical trial NCT04330547: Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness.
Official title: Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness: a Double-blind Placebo-controlled Clinical Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Disorders of Consciousness
Severe Brain Injury
Post-comatose Non-communicative Patients
Vegetative State
Minimally Conscious State
Keywords: Nociception
Pain
Disorder of Consciousness
Nociception coma scale revised
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2020-04-01
Enrollment: 19
Sex: ALL
Minimum age (years): 16
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to characterize and improve pain and nociception management in patients with disorders of consciousness (DOC). This project is divided into two phases, a first phase to evaluate pain level and a second phase which consist of a clinical trial to evalute pain medication efficacy.

The main aim is to evaluate the use of the Nociception Coma Scale-Revised (NCS-R) and its cut-off score (i.e., 5) as an assessment and management tool to define guidelines for managing pain in patients with DOC. In this double-blind, placebo-controlled clinical study, we will evaluate the use of analgesic treatments in reducing pain in subacute/chronic patients. The project will also allow us to validate the NCS-R cut-off score defined previously.

Detailed description: The study will be performed within one week (i.e, 7 days) and consists of two phases:

* Phase 1 "Patients selection (D0)": Patients will be assessed by the NCS-R during experimental stimulation (rest, tactile, noxious) and mobilizations (physiotherapy). Patients with potential pain will be included in the phase 2.
* Phase 2 "Analgesic administration (D1 and D2)": double-blind placebo-controlled randomized clinical trial on potential responders identified in phase 1. A medical doctor of our team will suggest to the physician in charge to prescribe the dedicated medication. One placebo and one real treatment will be administered on day 1 and 2 by the nurses at least half-hour before the physiotherapy. Randomization between day 1 and 2 will be applied at that time.

For each day of phase 1 and 2, several assessments will be performed: NCS-R, CRS-R and spasticity assessment.

Eligibility criteria: Inclusion Criteria:

* Have had an acquired brain injury with a loss of consciousness \> 28 days (patients) or have no history of previous brain injury (healthy controls)
* Legally authorized surrogate available to provide informed consent.
* Diagnosis of vegetative/unresponsive (VS/UWS) or minimally conscious state (MCS) or emergence of the minimally conscious state without communication (eMCS; as defined by the CRS-R, see above).
* Medically stable (i.e., no systemic illness or disease).
* Patients with NCS-R score during mobilization above or equal to the previously determined cut-off score or NCS-R scores during mobilization equivalent to NCS-R score obtain during nociceptive stimulation will be included in the second phase of the study (i.e. D1 and D2).

Exclusion Criteria:

* History of developmental, neurologic, or major psychiatric disorder resulting in functional disability.
* Contraindication or unwillingness to discontinuing sedating and centrally-active drugs (benzodiazepine, long-acting sedating drugs) within 48 hours of assessment.
* Upper limb contusions, fractures or flaccid paralysis.
* Uncontrolled epilepsy and already on level 1 drugs

Primary outcomes:
measure: Nociception Coma Scale-Revised (NCS-R)
timeFrame: through study completion, an average of 2 years
measure: Coma Recovery Scale-Revised (CRS-R)
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: Modified Ashworth Scale (MAS)
timeFrame: through study completion, an average of 2 years
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
Study officials:
affiliation: Centre du Cerveau, Coma Science Group (GIGA Consciousness)
name: Steven Laureys, M.D., P.h.D
role: STUDY_DIRECTOR
References:
citation: Ventafridda V, Saita L, Ripamonti C, De Conno F. WHO guidelines for the use of analgesics in cancer pain. Int J Tissue React. 1985;7(1):93-6.
citation: Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.
citation: Bohannon RW, Larkin PA, Smith MB, Horton MG. Relationship between static muscle strength deficits and spasticity in stroke patients with hemiparesis. Phys Ther. 1987 Jul;67(7):1068-71. doi: 10.1093/ptj/67.7.1068.
citation: Chatelle C, Majerus S, Whyte J, Laureys S, Schnakers C. A sensitive scale to assess nociceptive pain in patients with disorders of consciousness. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1233-7. doi: 10.1136/jnnp-2012-302987. Epub 2012 Aug 20.