Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001480572
Ethics application status
Approved
Date submitted
2/12/2024
Date registered
18/12/2024
Date last updated
18/12/2024
Date data sharing statement initially provided
18/12/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Examining the biopsychosocial predictors of treatment response to propranolol-based reconsolidation therapy for trauma- and stressor-related (TSR) disorders.
Scientific title
Examining the biopsychosocial predictors of treatment response to propranolol-based reconsolidation therapy in adults for trauma- and stressor-related (TSR) disorders.
Secondary ID [1] 313505 0
None
Universal Trial Number (UTN)
Trial acronym
RT4T
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post traumatic stress disorder 335935 0
Condition category
Condition code
Mental Health 332521 332521 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
6-session course of reconsolidation blockade (i.e., oral propranolol treatment combined with script-driven trauma recall)

Once all eligibility criteria has been established, participants will be enrolled into the study, and provided with a participant ID number and card. Participants will be advised that they will be placed on a 4-week waitlist before starting the intervention phase to allow for participants to be their own control (i.e., within subjects control condition). If participants wait for 4 weeks before starting the intervention, their PTSD symptoms measured during the waitlist period reflect the "no-treatment" state. After completing the treatment, any improvements beyond what occurred during the waitlist period can be attributed more confidently to the intervention.

Drug Trial
Low-dose oral tablet propranolol (Inderal®) treatment (40mg) administered once per week, for 6 weeks, approximately 90 minutes before each session.

Session 1 will take approximately 50 minutes and be delivered by a trained mental health clinician (i.e., psychologist/mental health social worker). Session 1 involves orienting the participant to the reconsolidation blockage processes and what to expect over the next 6 weeks of treatment. Participants will have been advised to take their first dose of propranolol on arrival, and the study General Practitioner will be onsite should any adverse events occur. The participant and practitioner will work together to identify the core trauma memory for the intervention and the participant will be invited to complete a script driven recall of the event. Once completed, the participant will be advised of their scheduled appointments and reminded of any key information to complete before their next session (i.e., when to take the dose of propranolol). If no adverse effects were observed or reported, the participant can leave the premises.

Sessions 2-6 will last approximately 25 minutes and involve a script recall exercise to activate the specific trauma memory targeted for that session.

All participants attendances/non-attendances will be captured using a session attendance checklist.
Intervention code [1] 330078 0
Treatment: Drugs
Intervention code [2] 330133 0
Treatment: Other
Comparator / control treatment
All participants will be advised that they will be placed on a 4-week waitlist before starting the intervention phase to allow for participants to be their own control (i.e., within subjects control condition).
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340040 0
The primary outcome of the study is a change in PTSD symptomatology.
Timepoint [1] 340040 0
Measured at several time points:
- T1 Baseline assessment (week 0)
- T3 post-treatment assessment (week 7 or 8)
- T5 Follow-up 2 (3 month)
Secondary outcome [1] 442747 0
Heart rate variability
Timepoint [1] 442747 0
T1 Baseline
T5 Follow Up 2 (3months post intervention)
Secondary outcome [2] 442748 0
Depression
Timepoint [2] 442748 0
T1 Baseline
T2 Pre-treatment (after 4-week waitlist)
T3 Post-treatment
T4 Follow up 1 (1 month post intervention)
T5 Follow up 2 (3 months post intervention)
Secondary outcome [3] 442749 0
Post-traumatic growth
Timepoint [3] 442749 0
T1 Baseline
T2 Pre-treatment (after 4-week waitlist)
T3 Post-treatment
T4 Follow up 1 (1 month post intervention)
T5 Follow up 2 (3 months post intervention)
Secondary outcome [4] 442750 0
Quality of Life
Timepoint [4] 442750 0
T1 Baseline
T3 Post treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [5] 442751 0
Sleep
Timepoint [5] 442751 0
T1 Baseline
T3 Post treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [6] 442752 0
Bloods:
Serum markers to measure (by ELISA assay or Luminex multiplex assay) - Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), inflammatory cytokines (including, but not necessarily limited to IL-1b, IL-2, IL-6, IL-8, IL-10, TNFa, IFNg), serotonin, kynurenine, tryptophan, FKBP51

Genotyping (from genomic DNA from blood) - single nucleotide polymorphisms (SNPs) from BNDF (including Val66Met - known PTSD risk factor), SNPs in beta-adrenergic receptors ADRB1, ADRB2, ADRB3 (binding receptors for propranolol), SNP within putative oestrogen response element within the pituitary adenylate cyclase–activating polypeptide (PACAP) type I receptor (PAC1) (ADCYAP1R1, SNP - rs2267735) (associates with PTSD diagnosis and symptoms in women), SNP upstream of an oestrogen receptor within histone deacetylase 4 (HDAC4, SNP – rs7570903) (associates to PTSD diagnosis and higher fear expression in women).
Timepoint [6] 442752 0
T2 Pre-treatment (after 4-week waitlist)
T3 Post-treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [7] 442753 0
Brain structure and activity - Exploratory outcome
Timepoint [7] 442753 0
T2 Pre-treatment (after 4-week waitlist)
T3 Post-treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [8] 442754 0
Various cognitive functions (e.g., attention, psychomotor speed, executive function
memory, learning, problem-solving)
Timepoint [8] 442754 0
T2 Pre-treatment (after 4-week waitlist)
T3 Post-treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [9] 442755 0
Saliva:
Measure oestrogen levels, alternative sample for cytokine measurements and genomic DNA for genotyping (if blood unable to be collected for any reason)
Timepoint [9] 442755 0
T2 Pre-treatment (after 4-week waitlist)
After each intervention session (Week 1 -6)
T3 Post-treatment
T5 Follow up 2 (3 months post intervention)
Secondary outcome [10] 442756 0
Hair:
Cortisol measurements (assayed from hair collected within 1-3 cm of scalp to determine average cortisol levels from 1-3 months prior)
Timepoint [10] 442756 0
T2 Pre-treatment (after 4-week waitlist)
T5 Follow up 2 (3 months post intervention)

Eligibility
Key inclusion criteria
Inclusion criteria:
- Persons aged 18 years +
- Participants must be able to understand Research Project Information Sheet (RPIS) and provide written informed consent on the Participant Informed Consent Form (PICF) (including both adequate intellectual capacity and fluency in English language)
- Diagnosis of PTSD
- Participants must undertake psychological, cognitive, and biological assessments, tolerate propranolol and not be taking any drugs that could contraindicate propranolol.
- Participants must have a current treating team who is managing their mental health diagnosis
- Persons of child-bearing potential must agree to use a *highly effective method of contraception

Highly effective methods of contraception are listed below:
- Hormonal methods of contraception including oral contraceptives containing combined estrogen and progesterone, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and progestogen-only hormonal contraception associated with inhibition of ovulation o Nonhormonal intrauterine device (IUD)
- Bilateral tubal occlusion
- Vasectomised participant/partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner.
- Abstinence from heterosexual intercourse: when this is in line with the preferred and usual lifestyle of the participant.

Periodic abstinence (e.g., calendar, ovulation, postovulation methods) and withdrawal are not acceptable methods of contraception. Persons in the following categories are not considered persons of childbearing potential
- Person without a uterus
- Premenarchal
- Premenopausal with permanent infertility due to 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
- Postmenopausal - A postmenopausal state is defined as no menses for 12 months without an alternative medical cause
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
- Complex PTSD
- Significant psychiatric condition: psychosis, bipolar disorder, personality disorder, substance use disorder
- Any contraindication to propranolol as determined by the study physician
- Development of serious, adverse, or unexpected events/reactions during the trial
- Previous allergy or reaction to propranolol, or other beta-adrenergic blocking agent
- Participation in any other clinical study at the time of enrolment, or having received any investigation product within 30 days of the day of enrolment onto the study
- Currently pregnant, breastfeeding or intending to become pregnant during the course of the study.
- Any other condition that, in the opinion of the investigator, may adversely impact the safety of the participant or the accuracy of the study data

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Statistical methods / analysis
Re-identifiable data (using the unique code identifiers) will be exported from Qualtrics to IBM SPSS for analysis. Statistical analyses will include generalised linear models (GLMs), analysis of the relative change index and frequentist statistics. A significance level of p <.05 (two-sided test) will be utilised where required. Data will be inspected for outliers and any spurious data will be corrected or removed prior to analysis. A detailed data analysis plan will be constructed by a statistician including the research questions and variables included. Missing data will be examined for missingness patterns. If the data is missing at random or completely at random, data imputation strategies may be employed in order to protect the integrity of this longitudinal sample and statistical power. Data will be analysed using descriptive, bivariate, and multivariate statistics using intent-to-treat analyses.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/01/2025
Actual
Date of last participant enrolment
Anticipated
4/10/2027
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 317954 0
Other
Name [1] 317954 0
Thompson Institute
Country [1] 317954 0
Australia
Primary sponsor type
Individual
Name
Dr Alain Brunet - University of the Sunshine Coast
Address
Country
Australia
Secondary sponsor category [1] 320291 0
Individual
Name [1] 320291 0
Dr Chris Moller - University of the Sunshine Coast
Address [1] 320291 0
Country [1] 320291 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316629 0
Human Research Ethics Committee of the University of the Sunshine Coast
Ethics committee address [1] 316629 0
Ethics committee country [1] 316629 0
Australia
Date submitted for ethics approval [1] 316629 0
14/10/2024
Approval date [1] 316629 0
25/11/2024
Ethics approval number [1] 316629 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 138462 0
Dr Alain Brunet
Address 138462 0
Thompson Institute (UniSC), 12 Innovation Parkway, Birtinya, 4575, QLD
Country 138462 0
Australia
Phone 138462 0
+61 754301191
Fax 138462 0
Email 138462 0
abrunet@usc.edu.au
Contact person for public queries
Name 138463 0
Trish Wilson
Address 138463 0
Thompson Institute (UniSC), 12 Innovation Parkway, Birtinya, 4575, QLD
Country 138463 0
Australia
Phone 138463 0
+61 754301191
Fax 138463 0
Email 138463 0
twilson2@usc.edu.au
Contact person for scientific queries
Name 138464 0
Dr Alain Brunet
Address 138464 0
Thompson Institute (UniSC), 12 Innovation Parkway, Birtinya, 4575, QLD
Country 138464 0
Australia
Phone 138464 0
+61 754301191
Fax 138464 0
Email 138464 0
abrunet@usc.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24396Study protocol  twilson2@usc.edu.au 388851-(Uploaded-10-12-2024-10-32-52)-HRE-Protocol-Project-Description (Version 2.1)_.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.