Efficacy Study of NH001 in Vegetative State & Minimally Conscious State Following a Traumatic Brain Injury - Full Text View

Sponsored by:	FDA Office of Orphan Products Development
Information provided by:	FDA Office of Orphan Products Development
ClinicalTrials.gov Identifier:	NCT00761228

Purpose

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

Condition	Intervention	Phase
Brain Injury	Drug: Apomorphine Drug: Placebo	Phase II

MedlinePlus related topics: Rehabilitation Traumatic Brain Injury

Drug Information available for: Apomorphine hydrochloride Apomorphine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Double-Blind, Placebo-Controlled, Randomized Study of the Safety and Efficacy of NH001 in Improving the Functional Outcome of Patients in a Vegetative State or Minimally Conscious State Following a Severe Traumatic Brain Injury

Further study details as provided by FDA Office of Orphan Products Development:

Primary Outcome Measures:

Presence or absence of meaningful responses to external commands based on Coma Recovery Scale-Revised [ Time Frame: Day 42 or the day that the drug treatment is discontinued, whichever happens earlier. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Baseline, weekly during drug treatment and at follow up visits of days 90,180 and 360. ] [ Designated as safety issue: No ]

Estimated Enrollment:	76
Study Start Date:	November 2008
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Apomorphine: Active Comparator Patients will receive an ascending dosing schedule to reach a maximum infusion rate of 6 mg/hour for 12 hours a day.	Drug: Apomorphine Patients will receive an ascending dosing schedule of continuous subcutaneous apomorphine to reach a maximum infusion rate of 6 mg/hour for 12 hours a day.
Placebo: Placebo Comparator Patients will receive a continues subcutaneous infusion of saline solution.	Drug: Placebo Patients will receive a continues subcutaneous infusion of saline solution.

Detailed Description:

This is a prospective, multi-center, randomized, double-blind, placebo-controlled study of the safety and efficacy of NH001 to improve the functional outcome of patients in a vegetative state or minimally conscious state following a severe TBI.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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 or any known neurostimulant (methylphenidate, amphetamines, atomoxetine, modafinil) within the last 7 days.
Patients who are receiving dopamine blockers (haloperidol, valproate)
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.
Patients receiving prophylactic anti-convulsive medications.
Patients with known allergies to apomorphine, morphine, sulfites or trimethobenzamide.
Patients who are receiving nitrates or other vasodilators.
Patients receiving CNS acting agents such as barbiturates, morphine, belladonna, opiates.
For male patients, patients who are receiving trazadone or any other drug that is known to produce priapism.
Patients without a relative or legal guardian to consent to the study.
Patients who, according to the investigator's opinion, are unlikely to be available for the required 180-day follow up evaluation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761228

Contacts

Contact: Daniel Katzman

617.331.4111

daniel@neurohealing.com

Locations

United States, Massachusetts
Spaulding Rehabilitation Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

FDA Office of Orphan Products Development

Investigators

Principal Investigator:	Elkan R Gamzu, PhD	NeuroHealing Pharmaceuticals Inc.
Principal Investigator:	Ross D Zafonte, DO	Spaulding Rehabilitation Hospital

More Information

Responsible Party:	NeuroHealing Pharmaceuticals ( Elkan Gamzu, Interim Head of Clinical Trials )
Study ID Numbers:	3337
Study First Received:	September 26, 2008
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00761228
Health Authority:	United States: Food and Drug Administration

Keywords provided by FDA Office of Orphan Products Development:

Vegetative State
Minimally Conscious State
Coma
Traumatic Brain Injury

Unconsciousness
Vegetative State secondary to a Traumatic Brain Injury
Minimally Conscious State secondary to a Traumatic Brain Injury

Study placed in the following topic categories:

Persistent Vegetative State
Craniocerebral Trauma
Unconsciousness
Brain Damage, Chronic
Consciousness Disorders
Wounds and Injuries
Central Nervous System Diseases
Disorders of Environmental Origin
Trauma, Nervous System

Brain Diseases
Apomorphine
Coma
Signs and Symptoms
Dopamine
Neoplasm Metastasis
Neurologic Manifestations
Brain Injuries
Neurobehavioral Manifestations

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases

Antiparkinson Agents
Dopamine Agents
Dopamine Agonists
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009