Efficacy Study of NH001 in Vegetative State & Minimally Conscious State Following a Traumatic Brain Injury

NCT00761228 | Suspended Phase 2 DMC

• 1 other identifier: 3337
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the drug apomorphine in subjects who are in a Vegetative State or a Minimally Conscious State.

Conditions

Brain Injury

Keywords

Vegetative State; Minimally Conscious State; Coma; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Presence or absence of meaningful responses to external commands based on Coma Recovery Scale-Revised

  Day 42 or the day that the drug treatment is discontinued, whichever happens earlier.

Secondary Outcomes (1)

• Coma/Near Coma Scale (CNC) Disability Rating Scale (DRS), Glasgow Outcome Scale Extended (GOS-E), ability to participate in 3 hours a day of active rehabilitation, and a clinical impression of change.

  Baseline, weekly during drug treatment and at follow up visits of days 90,180 and 360.

Study Arms (2)

Apomorphine

ACTIVE COMPARATOR

Patients will receive an ascending dosing schedule to reach a maximum infusion rate of up to 6 mg/hour for 12 hours a day.

Drug: Apomorphine

Placebo

PLACEBO COMPARATOR

Patients will receive a continues subcutaneous infusion of saline solution.

Drug: Placebo

Interventions

Apomorphine DRUG

Patients will receive an ascending dosing schedule of continuous subcutaneous apomorphine to reach a maximum infusion rate of up to 6 mg/hour for 12 hours a day.

Apomorphine

Placebo DRUG

Patients will receive a continues subcutaneous infusion of saline solution.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient is between 18 and 50 years of age, inclusive.
• Male or non-pregnant female (females of child-bearing potential will be required to have undergone a pregnancy test with negative results prior to entry to the study).
• Patients will have sustained a severe closed head injury within one to four months.
• Patients will have remained in a vegetative or minimally conscious state between one and four months after injury.
• Patients will have reached a stabilized clinical state prior to admission to the study (e.g. afebrile, haemodynamic and electrolyte stability).
• Patients will have a mean DRS score between 17 and 29, when measured twice a day over two consecutive days.
• Informed consent from a legal representative will have been obtained, according to the procedures outlined in Section 8.1.2.
• Patients who, according to the investigator's opinion, are likely to be available for the required 180-day follow up evaluation.

You may not qualify if:

• Patients who are not clinically stable at the time of entry into the study (infections, cardiovascular decompensation, etc.)
• Patients who require mechanical respiratory assistance.
• Patients who show signs of progressive neurological deterioration post-TBI.
• Patients with a known history of medically relevant substance abuse.
• Patients with history of cardiac disease.
• Patients who suffered an anoxic event.
• Patients who have received an investigational drug within 30 days of the study.
• Patients who have previously used NH001, other dopaminergic agent (e.g. levodopa, amantadine, domperidone) or any known neuro-stimulant (e.g. methylphenidate, amphetamines, atomoxetine, modafinil) within the last 7 days days.
• Patients who are receiving dopamine blockers (e.g. risperidone, haloperidol, chlorpromazine, flupenthixol, clozapine, olanzapine, quetiapine)
• Patients who are receiving drugs of the 5HT3 antagonist class, including, for example, ondansetron, granisetron, dolasetron, palonosetron and alosetron.
• Patients who are receiving tricyclic antidepressants drugs
• Patients who are receiving type I antiarrhythmics (i.e. quinidine).
• Patients who have a known history of cardiac arrhythmias or congenital QTc prolongation.
• Patients who have a known history of previous neurological functional impairment (e.g. stroke, spinal cord injury, dementia, epilepsy, psychiatric diseases).
• Patients who experienced seizures within the first week post injury or have ongoing seizures.

Sponsors & Collaborators

• NeuroHealing Pharmaceuticals Inc.: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

Spaulding Rehabilitation Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Brain Injuries; Persistent Vegetative State; Coma; Brain Injuries, Traumatic

Interventions

Apomorphine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• Elkan R Gamzu, PhD

  NeuroHealing Pharmaceuticals Inc.

  PRINCIPAL INVESTIGATOR

• Ross D Zafonte, DO

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2008
• First Posted: September 29, 2008
• Study Start: July 1, 2010
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 31, 2017

Record last verified: 2017-03

Locations

US (1)