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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

Tracking Information
First Submitted Date  ICMJE May 23, 2016
First Posted Date  ICMJE August 19, 2016
Last Update Posted Date November 6, 2017
Actual Study Start Date  ICMJE November 2016
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 16, 2016)
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).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Tolerability of Valproic Acid in Trauma Patients(Part 2)
Official Title  ICMJE 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)
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.

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Shock,Hemorrhagic
  • Trauma
Intervention  ICMJE
  • Drug: Valproic Acid
    By infusion over 1 hour
    Other Name: Depacon
  • Drug: Isotonic saline solution
    By infusion over 1 hour
Study Arms  ICMJE
  • Experimental: Valproic acid (Depacon)
    Valproic acid by IV infusion over one hour
    Intervention: Drug: Valproic Acid
  • Placebo Comparator: Isotonic saline solution
    The placebo administered by IV infusion over 1 hour
    Intervention: Drug: Isotonic saline solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 31, 2017)
1
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2016)
12
Actual Study Completion Date  ICMJE September 29, 2017
Actual Primary Completion Date September 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02872428
Other Study ID Numbers  ICMJE HUM00067452
VPA-C-002 ( Other Grant/Funding Number: Department of Defense/ONR )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Hasan Alam, University of Michigan
Study Sponsor  ICMJE Dr. Hasan Alam
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hasan Alam, MD University of Michigan
PRS Account University of Michigan
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP