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

NCT ID: NCT01517711

Last Updated: 2022-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2015-08-31

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.

Conditions

Post-Traumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tramadol ER

Tramadol in an extended release formulation with an initial dosage of 100 mg daily, increased weekly over the next two weeks, as tolerated, to a maximum of 300 mg daily

Group Type: EXPERIMENTAL

Tramadol

Intervention Type: DRUG

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 capsule

Lactose encapsulated to match appearance of experimental drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

Other Intervention Names

Ultram® ER

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Geracioti, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

Countries

United States

References

Geracioti TD. Tramadol treatment of combat-related posttraumatic stress disorder. Ann Clin Psychiatry. 2014 Aug;26(3):217-21.

Reference Type: DERIVED

PMID: 25166484 (View on PubMed)

Other Identifiers

INTRuST-Tramadol

Identifier Type: -

Identifier Source: org_study_id