Defeating the giant with a slingshot: testing a new technology to fight the global trauma epidemic

• Register: ISRCTN
• Last refreshed on: 20 September 2021
• Main ID: ISRCTN34308454
• Date of registration: 12/04/2018
• Prospective Registration: No
• Primary sponsor: Douglas Mental Health University Institute
• Public title: Defeating the giant with a slingshot: testing a new technology to fight the global trauma epidemic
• Scientific title: Pre-reactivation propranolol therapy to reduce post-traumatic stress disorder in Nepalese torture survivors
• Date of first enrolment: 01/04/2013
• Target sample size: 50
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN34308454
• Study type: Interventional
• Study design: Single-center randomized controlled trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Nepal

Contacts

• Name: Daniel Saumier

• Name: Alain Brunet

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female 25-65 years old
2. Fluency in a Nepali language
3. Having experienced a potentially traumatic event according to the CAPS trauma list more than 6 months ago
4. Evidence of trauma-related distress, or impaired functioning, not present before the index event
5. Evidence that the candidate participant understands the study procedures
6. Signed informed consent form, OR a document signed by the site principal investigator attesting that consent was given orally in the presence of a witness

Exclusion criteria:
1. Resting heart rate < 60 Beats Per Minute
2. Resting systolic blood pressure < 100 mm Hg
3. A PCL score below 50.
4. A CGI severity score below 4 (Moderately ill)
5. Not meeting the criteria for chronic PTSD at the time of randomization (visit 2)
6. Currently suicidal (i.e. a score of 3 or 4 on item 7 on the HSCL) or homicidal
7. A history of congestive heart failure, hypoglycemic medication-requiring diabetes, chronic bronchitis, emphysema, or asthma
8. Acute morbidity that leads to disabilityand that requires immediate medical treatment (e.g., gastric acid disease)
9. Previous adverse reaction to a ß-adrenergic blocker
10. Presence of drugs of abuse, viz., alcohol, opiates, marijuana, cocaine, or amphetamines, as determined by collateral informants
11. Women of child-bearing potential who are not using an acceptable birth-control method, including abstinence (condoms will be provided for free)
12. Positive pregnancy test
13. Breastfeeding
14. Contra-indicating neuropsychiatric condition, e.g., current psychotic, bipolar, melancholic, memory problems or substance dependence or abuse disorder
15. Current use of medication that involve potentially dangerous interactions with propranolol, including, other ß-adrenergic blockers, anti-arrythmics, and calcium channel blockers
16. Potent P450 2D6 inhibitors will not be exclusionary, because participants will receive only a single day’s dose of propranolol under observation, so that build-up of plasma levels over time due to decreased metabolism will not be a problem
17. Current use of a medication that may involve potentially dangerous interactions with paroxetine, such as cimetidine, amitriptyline, desipramine, risperidone, atomoxetine, thioridazine, a MAOI, or pimozide


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Post-traumatic stress disorder
Mental and Behavioural Disorders
Post-traumatic stress disorder

Intervention(s)

This study aims to compare how well the memory reconsolidation blockade therapy works when compared to the current gold-standard in PTSD treatment: a selective serotonin reuptake inhibitor called paroxetine. In order to do this, participants will randomly be assigned to one of two groups: one will receive the memory reconsolidation blockade treatment over 6 weeks, while the other will receive a 12-week treatment by means of paroxetine.

Participants are randomized to one of the two treatment conditions according to a double-blind randomization schedule that was prepared by personnel who were not otherwise involved in the study. A block randomization schedule was used to randomize subjects into groups that result in equal sample sizes. This method was used to ensure a balance in sample size across groups over time. Block sizes were balanced with the predetermined group assignments, with a 50% probability of being assigned to either the paroxetine or propranolol group.

For the paroxetine arm, the dosage will be 20mg per day via oral administration. Participants receiving paroxetine will be treated for a 12-week period during which they will receive paroxetine once daily. However, participants who wish to continue can receive paroxetine for 3 more months.

The 6-week (once per week) reconsolidation memory blockade treatment consists of a dose of 1 mg/kg of propranolol, a synthetic beta-adrenergic receptor blocker, administered 90 minutes before a reading of the script describing the individual's traumatic experience. Propranolol is administered orally.

A 26-week post-baseline follow-up assessment will be conducted for all subjects. The total duration for the final follow-up for all treatmen

Primary Outcome(s)

The feasibility of memory reconsolidation blockade, measured by numbers of treatment completers, study adherence, and percentage of psychometric ratings completed, measured at one year after the recruitment start date

1. Traumatic events experienced, assessed using the clinician-administered PTSD scale (CAPS)-Trauma list at the first visit
2. Recalled peritraumatic responses, measured using the Peritraumatic Distress Inventory
3. PTSD symptoms, assessed using the self-report PTSD symptom checklist (PCL) prior to each traumatic memory reactivation session to cover the week elapsed since the last such session

Secondary Outcome(s)

1. Axis I morbidity and comorbidity: general psychiatric comorbidity measured with the Nepali version of the Hopkins Symptom Checklist. The WHODAS-2 is a disability assessment instrument based on the conceptual framework of the International Classification of Functioning, Disability, and Health. It will provide a global measure of disability and seven domain-specific scores. These measures will be taken prior to the treatment and after the 6-week treatment has been completed.
2. Global clinical improvement associated with changes in mental health status, assessed at each visit with the Clinical Global Impression scale prior to treatment, at every treatment session (once per week for 6 weeks), and after the treatment has been completed
3. Quality of life, assessed using the WHO Quality of Life-BREF prior to the intervention and after the intervention has been completed

Secondary ID(s)

PRPL005

Source(s) of Monetary Support

Grand Challenges Canada

Ethics review

Status:
Approval date:
Contact:

1. Douglas Institute Research Ethics Board, 06/02/2013, ref: 12/41 2. Tribhuvan University Teaching Hospital, 30/01/2013

Results

• Results available: Yes
• Date Completed: 01/02/2019