Efficacy Study of NH001 in Vegetative State & Minimally Conscious State Following a Traumatic Brain Injury (NH001-2)

This study has suspended participant recruitment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
NeuroHealing Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT00761228
First received: September 26, 2008
Last updated: April 25, 2013
Last verified: April 2013
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by NeuroHealing Pharmaceuticals Inc.:

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: July 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Apomorphine
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
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.
Placebo Comparator: Placebo
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 traumatic brain injury (TBI).

  Eligibility

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

Inclusion Criteria:

  1. Patient is between 18 and 50 years of age, inclusive.
  2. 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).
  3. Patients will have sustained a severe closed head injury within one to four months.
  4. Patients will have remained in a vegetative or minimally conscious state between one and four months after injury.
  5. Patients will have reached a stabilized clinical state prior to admission to the study (e.g. afebrile, haemodynamic and electrolyte stability).
  6. Patients will have a mean DRS score between 17 and 29, when measured twice a day over two consecutive days.
  7. Informed consent from a legal representative will have been obtained, according to the procedures outlined in Section 8.1.2.
  8. Patients who, according to the investigator's opinion, are likely to be available for the required 180-day follow up evaluation.

Exclusion Criteria:

  1. Patients who are not clinically stable at the time of entry into the study (infections, cardiovascular decompensation, etc.)
  2. Patients who require mechanical respiratory assistance.
  3. Patients who show signs of progressive neurological deterioration post-TBI.
  4. Patients with a known history of medically relevant substance abuse.
  5. Patients with history of cardiac disease.
  6. Patients who suffered an anoxic event.
  7. Patients who have received an investigational drug within 30 days of the study.
  8. 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.
  9. Patients who are receiving dopamine blockers (e.g. risperidone, haloperidol, chlorpromazine, flupenthixol, clozapine, olanzapine, quetiapine)
  10. Patients who are receiving drugs of the 5HT3 antagonist class, including, for example, ondansetron, granisetron, dolasetron, palonosetron and alosetron.
  11. Patients who are receiving tricyclic antidepressants drugs
  12. Patients who are receiving type I antiarrhythmics (i.e. quinidine).
  13. Patients who have a known history of cardiac arrhythmias or congenital QTc prolongation.
  14. Patients who have a known history of previous neurological functional impairment (e.g. stroke, spinal cord injury, dementia, epilepsy, psychiatric diseases).
  15. Patients who experienced seizures within the first week post injury or have ongoing seizures.
  16. Patients receiving prophylactic anti-convulsive medications.
  17. Patients with known allergies to apomorphine, morphine, sulfites or trimethobenzamide.
  18. Patients who are receiving nitrates or other vasodilators.
  19. Patients receiving CNS acting agents such as barbiturates, morphine, belladonna, opiates.
  20. For male patients, patients who are receiving trazodone or any other drug that is known to produce priapism.
  21. Patients without a relative or legal guardian to consent to the study.
  22. Patients who, according to the investigator's opinion, are unlikely to be available for the required 180-day follow up evaluation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
Spaulding Rehabilitation Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
NeuroHealing Pharmaceuticals Inc.
Investigators
Principal Investigator: Elkan R Gamzu, PhD NeuroHealing Pharmaceuticals Inc.
Principal Investigator: Ross D Zafonte, DO Spaulding Rehabilitation Hospital
  More Information

No publications provided

Responsible Party: NeuroHealing Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00761228     History of Changes
Other Study ID Numbers: 3337
Study First Received: September 26, 2008
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by NeuroHealing Pharmaceuticals Inc.:
Vegetative State
Minimally Conscious State
Coma
Traumatic Brain Injury

Additional relevant MeSH terms:
Brain Injuries
Brain Damage, Chronic
Persistent Vegetative State
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Apomorphine
Emetics
Physiological Effects of Drugs
Pharmacologic Actions
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014