Tramadol Extended-Release (ER) for Posttraumatic Stress Disorder (PTSD)

Post-Traumatic Stress Disorder Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Flexible-Dose Pilot Clinical Trial of Once-Daily Extended-Release Tramadol for the Treatment of PTSD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01517711
• Other study ID #: INTRuST-Tramadol
• Status: Completed
• Phase: Phase 4
• Start date: September 2011
• Est. completion date: August 2015

Study information

• Verified date: August 2022
• Source: INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Post-Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Tramadol
Tramadol hydrochloride Extended Release(ER) will be supplied as tablets of Ultram® ER 100mg. Tramadol ER (100-300mg) or matching placebo will be self-administered by oral route every morning (with or without food) for 6 weeks. Patients will be instructed to take it the same way (either with food or without food) each time they take their dose. Each patient will be provided with 1 week supply of Tramadol ER or matching placebo on visits 2 (week 0) and 3 (week 1) and 2 weeks supply on visits 4 (week 2) and 5 (week 4).
• Placebo
Matching placebo will be self-administered by oral route every morning (with or without food) for 6 weeks. Patients will be instructed to take it the same way (either with food or without food) each time they take their dose. Each patient will be provided with 1 week supply of Tramadol ER or matching placebo on visits 2 (week 0) and 3 (week 1) and 2 weeks supply on visits 4 (week 2) and 5 (week 4).

Locations

Country	Name	City	State
United States	Cincinnati VA Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium	U.S. Army Medical Research and Development Command

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinician-Administered PTSD Scale (CAPS)	The Clinician-Administered PTSD Scale (CAPS) is an interview-based measure of severity of PTSD symptoms. A total score is calculated with a range of 0-136, with higher numbers indicating more severe symptoms.	Weeks 0 (baseline),1, 2, 4, 6
Primary	Clinical Global Impression -- Improvement (CGI-I) -- Subject	The Clinicial Global Impression - Improvement (CGI-I) is a single item rated by a clinician. The range is 1 (very much improved)) to 7 (very much worse).	Week 6, assessing clinician's judgment of change from week 0 to week 6
Secondary	Visual Analog Scales (VAS)	Self-rated 100-mm visual analog scales [0 to 100 scale; higher score indicates more of the rated state] to rate poor sleep, happiness, irritability, nervousness and pain. Change is calculated by subtracting week 6 from week 0.	Change from week 0 to 6
Secondary	Quick Inventory of Depressive Symptoms (QIDS)	Quick Inventory of Depressive Symptoms - Self Report (QIDS) is a self-report scale of severity of depression. A total score is calculated with a range of 0 to 27, with higher numbers indicating greater severity.	Weeks 0, 1, 2, 4 and 6