Shock,HemorrhagicPhase 1NCT02872428
A Study to Evaluate the Safety and Tolerability of Valproic Acid in Trauma Patients(Part 2)
A Phase 1 study testing Valproic Acid and Isotonic saline solution in people with Shock,Hemorrhagic and Trauma, run by Dr. Hasan Alam at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Shock,Hemorrhagic, Trauma
- What is being tested?
- Valproic Acid and Isotonic saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2016to 29 Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
- -
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Michigan
Ann Arbor, Michigan, 48109
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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)
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.
Read the 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).
- Conditions
- Shock,Hemorrhagic, Trauma
- Being tested
- Valproic Acid, Isotonic saline solution
- Medical subject headings
- Shock, Hemorrhagic, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Also called Depacon
By infusion over 1 hour
Isotonic saline solutionDrug
By infusion over 1 hour
| Study group | Role | What they receive |
|---|---|---|
| Valproic acid (Depacon) | Experimental | Valproic acid by IV infusion over one hour Receives: Drug: Valproic Acid |
| Isotonic saline solution | Placebo comparator | The placebo administered by IV infusion over 1 hour Receives: Drug: Isotonic saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2016 (estimated)
- Study startNov 2016
- Primary completion29 Sep 2017
- Study completion29 Sep 2017
Why it stopped: at request of funding group because of failure to enroll more than one patient
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Shock,HemorrhagicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Hasan Alam
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Hasan Alam, University of Michigan
- Investigators
- Hasan Alam, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02872428
- Sponsor's protocol ID
- HUM00067452
- Other IDs
- VPA-C-002
- Status last verified
- Oct 2017
- First submitted
- 23 May 2016
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02872428
- Acronym / sponsor ID
- HUM00067452
- Conditions
- Shock,Hemorrhagic, Trauma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: at request of funding group because of failure to enroll more than one patient
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Dr. Hasan AlamUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- 29 Sep 2017 (actual)
- Study completion
- 29 Sep 2017 (actual)
- First posted
- 19 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valproic acid (Depacon) | Experimental | Drug: Valproic AcidValproic acid by IV infusion over one hour |
| Isotonic saline solution | Placebo comparator | Drug: Isotonic saline solutionThe placebo administered by IV infusion over 1 hour |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic AcidAlso: DepaconBy infusion over 1 hour | Drug | Valproic acid (Depacon) |
| Isotonic saline solutionBy infusion over 1 hour | Drug | Isotonic saline solution |
Primary outcome
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).
Results and safety
The study was stopped early (reason given: at request of funding group because of failure to enroll more than one patient). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hasan Alam, MD principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Valproic Acid and Isotonic saline solution in people with Shock,Hemorrhagic and Trauma, run by Dr. Hasan Alam at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: at request of funding group because of failure to enroll more than one patient). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.