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A Study to Evaluate the Safety and Tolerability of Valproic Acid in Trauma Patients(Part 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02872428
Recruitment Status : Terminated (at request of funding group because of failure to enroll more than one patient)
First Posted : August 19, 2016
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
Dr. Hasan Alam, University of Michigan

Brief Summary:

THIS IS THE SECOND PART OF A 2-PART STUDY. The purpose of the first part of this study was to determine the safety and tolerability of ascending doses of valproic acid (also known as Depacon) administered as intravenous infusion (IV) in doses ranging from 15 mg/kg to 250 mg/kg in healthy subjects.

ID: VPA-C-002

The second part of the study will also be to determine the safety and tolerability of single ascending doses of valproic acid administered as IV in trauma subjects with hemorrhagic shock.


Condition or disease Intervention/treatment Phase
Shock,Hemorrhagic Trauma Drug: Valproic Acid Drug: Isotonic saline solution Phase 1

Detailed Description:

THIS IS THE SECOND PART OF A 2-PART STUDY. Part 1 of the study will be a single center study intended to assess the safety and tolerability of valproic acid dosages at 15 mg/kg, 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, 150 mg/kg 180 mg/kg, 210 mg/kg and 250 mg/kg. Up to 72 healthy subjects (9 dose groups of 8 subjects) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 3:1 active drug: placebo. ID: VPA-C-002

Part 2 of the study will be a multi-center, double blind, placebo-controlled study in trauma patients with hemorrhagic shock. The patients will be able to consent themselves, or if unable due to injuries, a Legally Authorized Representative will consent for them. Up to 12 patients (2 dose groups of 6 patients) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 2:1 active drug : placebo. The dose levels in Part 2 will be the two highest doses that are demonstrated to have acceptable safety profile based on the review of safety data from Part 1 (130mg/kg and 140mg/kg).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Single Ascending Dose, Double Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1) or Trauma Patients(Part 2)
Actual Study Start Date : November 2016
Actual Primary Completion Date : September 29, 2017
Actual Study Completion Date : September 29, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Valproic acid (Depacon)
Valproic acid by IV infusion over one hour
Drug: Valproic Acid
By infusion over 1 hour
Other Name: Depacon

Placebo Comparator: Isotonic saline solution
The placebo administered by IV infusion over 1 hour
Drug: Isotonic saline solution
By infusion over 1 hour




Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) [ Time Frame: As this is a safety study, subjects will be monitored for side-effects beginning immediately after the one hour infusion until the follow-up visit (between 2-6 weeks post infusion) is completed. ]

    Dose limiting toxicity (DLT) will be measured by drug-related grade 2 (moderate) or higher

    toxicity indicators (excluding fever, chills, nausea or other possible infusion-related effects).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and non-pregnant female trauma patients between the ages of 18-70 years, inclusive.
  2. Blunt or penetrating trauma resulting in two or more systolic blood pressure readings of ≤ 110 mmHg at any point during transport to the hospital or within the first hour after arrival in the emergency department. Systolic blood pressure readings of ≤ 110 mmHg need not be consecutive (Eastridge et al., 2007).
  3. Patient's admission to the emergency department results in trauma team activation (per institutional criteria, see Appendix 7).
  4. Patient's injuries are considered potentially survivable by the attending trauma surgeon on initial evaluation.
  5. Able to provide informed consent or consent can be obtained from a representative (spouse or other legally authorized representative) in the event that the subject is unconscious or otherwise impaired.
  6. Female subjects must be postmenopausal, surgically sterilized, or have a negative urinary pregnancy test on arrival. Criteria for menopause include age > 45 with absence of menses for > 12 months. Criteria for surgical sterilization include hysterectomy and/or oophorectomy. Tubal ligation with menses within the past 12 months is not considered to be surgical sterilization.
  7. Body mass index (BMI) between 18 kg/m2 and 35 kg/m2

Exclusion Criteria:

  1. Subjects with known history of adverse reaction to Valproic acid.
  2. Subjects with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency.
  3. Subjects with -amylase >400 U/L or lipase >300 U/L or creatinine >ULN
  4. Subjects with AST or ALT >3X Upper limit of normal (ULN) or total bilirubin >1.5X Upper limit of normal (ULN)
  5. Subjects with 2nd or 3rd degree burns of any size and location.
  6. Female subjects who are pregnant or lactating.
  7. Subjects who are currently incarcerated.
  8. Subjects with severe traumatic brain injury (with Glasgow Coma Scale score <8 on arrival to the emergency department).
  9. Non-hemorrhagic causes of shock, including septic, cardiogenic, or neurogenic shock or mechanical reasons such as tension pneumothorax or cardiac temponade.
  10. Subjects with inadequate venous access.
  11. Subject with a hemoglobin level of less than 8g/dL.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02872428


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
The University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Dr. Hasan Alam
Investigators
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Principal Investigator: Hasan Alam, MD University of Michigan
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Responsible Party: Dr. Hasan Alam, Hasan Alam, MD, Norman Thompson Professor of Surgery Section Head, General Surgery, University of Michigan
ClinicalTrials.gov Identifier: NCT02872428    
Other Study ID Numbers: HUM00067452
VPA-C-002 ( Other Grant/Funding Number: Department of Defense/ONR )
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Shock, Hemorrhagic
Wounds and Injuries
Hemorrhage
Pathologic Processes
Shock
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs