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Perioperative Propranolol in Patients With Post Traumatic Stress Disorder (PTSD)

This study is currently recruiting participants.
Verified May 2013 by University of California, San Francisco
Sponsor:
Collaborators:
Department of Defense
Northern California Institute of Research and Education
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01555554
First received: March 5, 2012
Last updated: May 17, 2013
Last verified: May 2013
History of Changes
  Purpose

Understanding what treatments may facilitate perioperative care of Veterans with posttraumatic stress disorder (PTSD) is of great importance to the U.S. health care system.

Patients with PTSD are characterized by elevated central nervous system catecholamine concentrations and exaggerated and prolonged adrenergic responses to stress stimuli. At present, there are no data on the effects of perioperative beta blocker therapy in patients with PTSD, despite the rising significance of PTSD in Veteran populations.

This prospective, double-blind study proposes to randomize 150 Veterans with PTSD scheduled for orthopedic, thoracic or vascular surgery at the San Francisco VA Medical Center to either a 14-day course of propranolol or placebo. This study will then follow these Veterans for a one-year period to evaluate the effects of the intervention on Veterans' surgical outcomes.

The investigators hypothesize that patients with PTSD randomized to the propranolol group will demonstrate a reduced incidence of perioperative and postoperative morbidity and mortality.


Condition Intervention
Post-traumatic Stress Disorder
 Drug: Propranolol Hydrochloride
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of Prophylactic, Perioperative Propranolol on Peri- and Postoperative Complications in Patients With Post Traumatic Stress Disorder

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • ICU length of stay [ Time Frame: Truncated at 30 days after admission to ICU ] [ Designated as safety issue: Yes ]
    Measured using patient medical records

  • Hospital length of stay [ Time Frame: Truncated at 30 days after admission to ICU ] [ Designated as safety issue: Yes ]
    Measured using patient medical records

  • Postoperative delirium [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Measured using Confusion Assessment Method (CAM-CAM-ICU)

  • Postoperative renal dysfunction [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Measured using Serum Creatinine laboratory values


Secondary Outcome Measures:
  • Perioperative complications [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Measured using patient medical records

  • Pain intensity [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Numerical Rating Scale

  • Pain unpleasantness [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Numerical Rating Scale

  • Analgesics use [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Length of intubation and mechanical ventilation [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week ] [ Designated as safety issue: Yes ]
    Measured using patient medical records

  • Post Traumatic Stress Disorder symptomatology [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Clinician Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS)

  • Quality of Life [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using Short Form-36 Questionnaire (SF-36)

  • Functional status [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using Short Form-36 Questionnaire (SF-36)

  • Sleep Quality [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Pittsburgh Sleep Quality Index (PSQI)

  • Depression symptoms [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Beck Depression Inventory (BDI)

  • Postoperative Neurocognitive Dysfunction Score [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using the Mini Mental State Examination (MMSE)

  • 30-day, 3-month, and 1-year mortality [ Time Frame: Participants will be followed from preoperative baseline to 1 year postoperative ] [ Designated as safety issue: No ]
    Measured using patient medical records

  • Postoperative complications [ Time Frame: Participants will be followed to 1 year postoperative ] [ Designated as safety issue: Yes ]
    Measured using patient medical records


Estimated Enrollment: 110
Study Start Date: May 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Propranolol Hydrochloride Drug: Propranolol Hydrochloride

Propranolol will be taken for a total of 14 days. On the morning of the surgery, prior to entry into the operating room, patients will receive the first dose of the study drug (the PDR recommended starting dose of Propranolol XL- Extended Release). Patients will take one 60 mg pill on the morning of surgery.

On post operative day #1, patients will take one pill of receive propranolol XL 80 mg (once daily by mouth).

On post operative days #2-#9, patients will take one pill of propranolol XL 120 mg (once daily by mouth).

On post operative days #10-11, patients will take one pill of propranolol XL 80 mg (once daily by mouth).

On post operative days #12-13, patients will take one pill of propranolol XL 60 mg (once daily by mouth).

This will complete the course of propranolol.

Other Names:
  • Inderal
  • Inderal LA
  • Avlocardyl
  • Avlocardyl Retard
  • Deralin
  • Dociton
  • Inderalici
  • InnoPran XL
  • Sumial
  • Anaprilinum
  • Bedranol SR Sandoz
Placebo Comparator: Placebo Group Other: Placebo

The placebo pill will be taken for a total of 14 days. On the morning of the surgery, prior to entry into the operating room, patients will receive the first placebo pill to be taken once daily by mouth.

On post operative days #1-13, patients will take one placebo pill (once daily by mouth).

This will complete the course of the placebo.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects scheduled for any surgical procedure under general anesthesia or combined general-regional anesthesia, with the exception of open-heart or intracranial surgery. Regional anesthesia includes: 1) Epidural anesthesia, 2) Sub-arachnoid block (spinal), or 3)any regional nerve block
  2. Anticipated postoperative hospital admission (defined as at least one overnight hospital stay)
  3. Subjects positive for full or subthreshold PTSD of at least 3 months duration as indexed by a total score of 30 or higher on the Clinician Administered PTSD Scale (CAPS)

Exclusion Criteria:

Veterans will be excluded if:

  1. They are on beta blocker therapy at the time of the preoperative baseline assessment
  2. They report sensitivity or allergies to propranolol, or a history of PTSD exacerbation with prior propranolol therapy
  3. Veterans who fulfill the AHA/ACC level I recommendation criteria for perioperative beta blocker therapy (e.g., metoprolol, atenolol) and should not be randomized to placebo group
  4. Medical exclusions criteria: high grade heart block without pacemaker (all patients with 2nd and 3rd degree heart block), marked resting bradycardia (heart rate ≤ 55 beats per minute), blood pressure < 100 mmHg, uncompensated congested heart failure, severe hyperactive airway disease, Raynaud's disease, and head injury [head trauma requiring hospitalization documented in the medical chart or reported by patient]
  5. Pregnancy
  6. Prominent suicidal or homicidal ideations
  7. Current use of medication that may involve potentially dangerous interaction with propranolol
  8. A current alcohol dependence or substance dependence diagnosis as evidenced by findings on the SCID assessment,
  9. Circumstances that, in the opinion of the principal investigator, would preclude participation in a study of this type (e.g. medical concerns or difficulty in long-term followup).
  10. Open-heart surgery and intracranial surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01555554

Contacts
Contact: Marek Brzezinski, M.D., Ph.D. 877-487-2838 brzezinm@anesthesia.ucsf.edu
Contact: Curt Johanson, B.A. (415) 221-4810 ext 5957 curt.johanson@va.gov

Locations
United States, California
San Francisco VA Medical Center Recruiting
San Francisco, California, United States, 94121
Principal Investigator: Marek Brzezinski, M.D., Ph.D.            
Sub-Investigator: Hubert Kim, MD            
Sub-Investigator: Thomas Neylan, M.D.            
Sub-Investigator: Kristin Samuelson, Ph.D.            
Sub-Investigator: Arthur Wallace, M.D. Ph.D.            
Sponsors and Collaborators
University of California, San Francisco
Department of Defense
Northern California Institute of Research and Education
Investigators
Principal Investigator: Marek Brzezinski, M.D., Ph.D. University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01555554     History of Changes
Other Study ID Numbers: W81XWH-10-2-0078
Study First Received: March 5, 2012
Last Updated: May 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Post-traumatic stress disorder
Propranolol
surgery
anesthesia

Additional relevant MeSH terms:
Postoperative Complications
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Pathologic Processes
Anxiety Disorders
Mental Disorders
Propranolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
 Pharmacologic Actions
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents

ClinicalTrials.gov processed this record on June 17, 2013