Clinical trial NCT01517711: Tramadol Extended-Release (ER) for Posttraumatic Stress Disorder (PTSD)
Official title: A Double-Blind, Placebo-Controlled, Flexible-Dose Pilot Clinical Trial of Once-Daily Extended-Release Tramadol for the Treatment of PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Post-Traumatic Stress Disorder
Keywords: pharmacotherapy
combat disorders
Lead sponsor: INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2012-01-25
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a six-week pilot study testing the efficacy of tramadol extended-release (ER) for posttraumatic stress disorder (PTSD). Men and women aged 21-55 years with combat-related PTSD or PTSD resulting from a civilian trauma were recruited. Blinded tramadol ER was begun with a 100 mg daily dose for the first week, with an option to increase to 200 mg/day for the 2nd week. Dose adjustments, using a range of 100-300 mg tramadol ER per day (or 1 to 3 placebo tabs), were permitted thereafter. The primary hypothesis was that tramadol ER 100 to 300 mg every morning for 6 weeks would reduce the symptoms of PTSD relative to placebo. The primary outcome measures were PTSD symptoms as rated by the Clinician-Administered PTSD Scale (CAPS) and Clinicians Global Impressions scale at baseline and weeks one, two, four, and six.

Detailed description: This was a single-site, double-blind, placebo-controlled, randomized, 6-week, parallel-group, flexible-dose outpatient trial of tramadol ER 100-300 mg once every morning for PTSD. Double-blinded clinical outcome measures were obtained during screening, and at weeks 0 (pre-randomization), 1, 2, 4, and 6; outcome was also assessed at week 7, the follow-up and study discharge visit, which occurred one week after the discontinuation of study medicine. Tramadol ER (or placebo) was started at 100 mg daily and increased weekly over the next two weeks, as tolerated, to a maximum of 300 mg daily. Dose change was also permitted at week 4. Matching drug and placebo were prepared by a research pharmacy using over-encapsulation in locking DB capsules supplied by Capsugel. Lactose was used as a filler to attain uniformity in weight. Randomization used a 1:1 allocation ratio and was via a block design, with stratification by military service. Other than the research pharmacists, all study personnel, all staff, and all subjects were blind.

Eligibility criteria: Inclusion Criteria:

1. Men and women, military veterans and non-veterans, aged 21-55 years
2. Active PTSD as determined by diagnostic evaluation and standardized interview (Structured Clinical Interview for the DSM (SCID))
3. Literacy and ability to give informed consent
4. In women of child-conceiving potential, a negative pregnancy test and use of an approved birth control method
5. Glasgow Coma Scale (GCS) score of 15, Extension of GCS with 7-point Amnesia Scale score of 6 (amnesia for traumatic event of 30 min or fewer) or 7 (no amnesia for impact of head) (Nell et al 2000)
6. Clinically judged to be at low risk for adverse sequelae from taking tramadol
7. Concomitant medications must be approved by the PI

Exclusion Criteria:

1. Pregnant or nursing women
2. Homeless persons
3. Suicidal or homicidal ideation with plans or intent
4. History of opioid dependence or abuse
5. Psychosis or history thereof, substance dependence or abuse (other than tobacco dependence; lifetime opioid abuse is exclusionary) within the past 60 days, anorexia nervosa, antisocial personality disorder, or other psychiatric disorder judged by the investigator to be more clinically significant than PTSD
6. Serious or unstable illness, endocrinopathy, or metabolic instability, including renal insufficiency, liver disease, hydrocephalus, history of stroke, history of seizures, history of brain tumor
7. Use of non-study medications except those approved by the PI
8. Newly started in psychotherapy (\< 3months)
9. History of hypersensitivity, allergy, or other significant adverse effects from tramadol

Primary outcomes:
measure: Clinician-Administered PTSD Scale (CAPS)
timeFrame: Weeks 0 (baseline),1, 2, 4, 6
measure: Clinical Global Impression -- Improvement (CGI-I) -- Subject
timeFrame: Week 6, assessing clinician's judgment of change from week 0 to week 6
Secondary outcomes:
measure: Visual Analog Scales (VAS)
timeFrame: Change from week 0 to 6
measure: Quick Inventory of Depressive Symptoms (QIDS)
timeFrame: Weeks 0, 1, 2, 4 and 6
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Thomas Geracioti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Geracioti TD. Tramadol treatment of combat-related posttraumatic stress disorder. Ann Clin Psychiatry. 2014 Aug;26(3):217-21.