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

NCT02872428 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: HUM00067452VPA-C-002
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 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.

Conditions

Shock,Hemorrhagic; Trauma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  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).

  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.

Study Arms (2)

Valproic acid (Depacon)

EXPERIMENTAL

Valproic acid by IV infusion over one hour

Drug: Valproic Acid

Isotonic saline solution

PLACEBO COMPARATOR

The placebo administered by IV infusion over 1 hour

Drug: Isotonic saline solution

Interventions

Valproic Acid DRUG

By infusion over 1 hour

Also known as: Depacon

Valproic acid (Depacon)

Isotonic saline solution DRUG

By infusion over 1 hour

Isotonic saline solution

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and non-pregnant female trauma patients between the ages of 18-70 years, inclusive.
• 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).
• Patient's admission to the emergency department results in trauma team activation (per institutional criteria, see Appendix 7).
• Patient's injuries are considered potentially survivable by the attending trauma surgeon on initial evaluation.
• 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.
• 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.
• Body mass index (BMI) between 18 kg/m2 and 35 kg/m2

You may not qualify if:

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

Sponsors & Collaborators

• Dr. Hasan Alam: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Shock, Hemorrhagic; Wounds and Injuries

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Hasan Alam, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Hasan Alam, MD, Norman Thompson Professor of Surgery Section Head, General Surgery

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: August 19, 2016
• Study Start: November 1, 2016
• Primary Completion: September 29, 2017
• Study Completion: September 29, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-10

Locations

US (2)