Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06193772 |
| Other study ID # |
SU-308-0226-23 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 26, 2024 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
April 2024 |
| Source |
Stockholm University |
| Contact |
Björn Philips, Ph.D. |
| Phone |
+48 8 162010 |
| Email |
bjorn.philips[@]psychology.su.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The overarching research project aims to evaluate of an internet-delivered affect-focused
psychodynamic treatment (IPDT) for adolescents aged 15-19 with depression. The previous study
was a non-inferiority randomized controlled trial (RCT) comparing IPDT with
internet-delivered cognitive behavior therapy (ICBT). The results showed that IPDT and ICBT
had similar effects. Adolescents in both treatments showed large improvements in both
depression and other outcome measures. Online psychological treatment is also known as guided
self-help, where the participant reads texts and performs exercises on their own, with the
support of an online therapist.
The planned study is an RCT to investigate the effect of therapist feedback and customized
treatment for adolescents at risk of not being helped by IPDT. The study builds on analyses
of predicted treatment trajectories in the project's previous study. Based on these analyses,
algorithms have been developed that identify which young people who, after three weeks of
treatment, are at risk of not getting a good outcome from the treatment. In the present
study, 240 young people aged 15-19 with major depression will begin IPDT. After three weeks
of treatment, the course of the treatment is analyzed using the algorithm and the young
people who are at risk of not having a good outcome are identified. These adolescents are
randomized to either continue unchanged treatment or to receive detailed therapist feedback
on the adolescent's treatment prognosis and instructions to adapt the treatment in
consultation with the individual adolescent. The IPDT treatment consists of eight modules and
treatment duration is ten weeks. The study evaluates the effect of the treatment on
depression and other variables such as anxiety symptoms, emotion regulation and self-image.
The project's previous studies have shown that IPDT is an effective treatment that can be
offered to adolescents with depression. The planned study can show whether the outcome of
IPDT can be further improved by paying attention to adolescents with poorer treatment
progress and adapting the treatment more to their needs.
Description:
Study goals and objectives This is the third study in a larger project, the ERiCA project.
The overarching aim of the project is to develop and evaluate cost-effective
internet-delivered treatments for adolescent depression. The present study will try an
adaptive treatment strategy with the goal of increasing treatment response rates. Based on
data from our previous large non-inferiority trial (Mechler et al., 2022), an algorithm have
been developed for prediction of treatment non-response at week 3. The specific objective of
the present trial is to evaluate whether identifying participants at risk of non-response and
then adapting treatment during the course of treatment can reduce risk of non-response.
Additional goals are to investigate process factors that predict and mediate outcome for the
treatment in order to learn more about mechanisms and processes of change and no-change.
Primary research question Research question 1: Can adapted treatment reduce risk of
non-response for identified at-risk-participants in IPDT? Hypothesis 1: Adapted treatment
will decrease risk of non-response in IPDT in comparison with non-adaptive treatment
strategy.
Research question 2: Can non-response be accurately predicted? Hypothesis 2: Non-response
will be accurately predicted using an algorithm at week 3.
Secondary research questions 3: Are there patient factors that affect efficacy of the
treatment program (i.e. predictors/moderators) and the adapted treatment program? 4: Are
there within-treatment factors that affect efficacy of the program and adaptation
(mediators)? 5. Are there differences in the effects on the severity of depressive symptoms,
anxiety symptoms, capacity for mentalized affectivity, emotion regulation, fear of negative
emotions, defense mechanisms, and self-concept when comparing adaptive treatment strategies
to non-adaptive?
Study Design The trial is a randomized controlled trial (RCT). All eligible participants (n =
240) will be entered into IPDT. At week 3 in treatment, participants at risk of non-response
will be identified using our open-source algorithm. Identified participants at risk will be
randomized to either adapted treatment or continued IPDT as usual.
Withdrawal criteria: Patients that deteriorate into becoming suicidal will be withdrawn from
the project and referred to psychiatric care. Data will be collected at baseline, multiple
time points (weekly) during treatment, as well as at follow up (6 and 12 months after
termination).
The trial is scheduled to take place between 2024 and 2025.
Study setting The project is based at Stockholm University. As treatment is conducted over
the internet, participants can be recruited nation-wide, giving opportunities for recruiting
a larger as well as a more heterogeneous sample regarding several aspects such as geographic
location and socioeconomic status. The project will use the well-developed infrastructure and
the secure Internet platform used in many studies conducted by Per Carlbring at Stockholm
University and Gerhard Andersson at Linköping University. The project is conducted in close
collaboration with professor Gerhard Andersson at Linköping University who has vast
experience in internet trials with adults as well as adolescents.
Intervention IPDT consists of 8 therapist-supported self-help modules delivered over 10 weeks
on a secure online platform. Modules consist of texts and video followed by assignments which
they send to their therapist and receive feedback within a few days.
The IPDT program has been developed specifically for this project and is based on similar
principles as a treatment with shown efficacy for adults in several RCTs. The aim of the
intervention is to decrease emotional avoidance and increase awareness and experience of
emotions. Participants are encouraged to approach previously warded off feelings. They will
also be taught how to link their emotional reactions to their symptoms. Another treatment
goal is to acquire a greater capacity for anxiety regulation. The final part of the program
contains material on how to express previously warded off affects in key relationships, in
order to improve the participant's relationships. Compared to the existing treatment for
adults, the modules in the age-adapted program for adolescents are shorter and easier to
read, with vignettes more recognizable for the age group. Latter parts of the material give
particular notice to developmental aspects especially relevant in adolescence.
Adapted treatment Participants randomized to adapted treatment are contacted by their
assigned therapist and given information about treatment modification. Changes are
implemented as of week 3 of treatment. The adaptations will be suggested by the therapist
from a treatment manual with the goal of personalizing treatment and facilitating treatment
engagement. The therapist and the participant will collaboratively agree on adaptations.
Examples of adaptations are: added weekly text-chat (30 min), added bi-weekly phone calls (30
min), reminders, and shortened chapters or less exercises.
Therapists The therapists will be master students in the Swedish clinical program in
psychology, in the final phase of their training as psychologists in which they have their
psychotherapy courses. The therapists in the project will be trained in IPDT and supervised
by an experienced psychologist. The therapists will be able to track patients' progress on
the measures administered weekly.
Outcomes Primary outcome will be response to treatment according to the proportion
improvement method (Hiller et al., 2012).
Research question 1 will be investigated by comparing the outcome of adapted IPDT for at-risk
patients with standard IPDT for at-risk patients.
Research question 2 will be investigated by comparing the outcome of standard IPDT for
on-track patients with standard IPDT for at-risk patients.
Furthermore, we will investigate possible predictors, moderators and mediators in terms of
capacity for mentalized affectivity, identity, fear of negative emotions, demographics,
expectations, symptom/distress profile, self-compassion and treatment alliance.
Participant timeline Participants contacting the project will be directed to an online
website where they can access further information about the project, give informed consent to
participate and subsequently get access to the screening forms for the trial. If fulfilling
inclusion criteria and not fulfilling exclusion criteria according to the screening forms, a
diagnostic telephone interview will be held, establishing fulfilment of inclusion criteria
and non-fulfilment of any exclusion criteria. Eligible participants will be asked to confirm
participation in the study, after which they will start in standard IPDT.
All instruments consist of online administered self-report questionnaires with proven
validity and reliability. Five of the self-rating scales will be administered weekly, for
tracking outcome and possible mediators. Two questionnaires will also be administered weekly
to the treating therapists for tracking potential mediators. Other questionnaires will be
administered only at baseline, termination and follow-up.
Sample size Power calculation focusing on the primary research question was made based on
binary outcomes (non-response/response) using Sealed Envelope. We based our power analysis on
the results of adapted treatment in Forsell et al. (2019), where adapted treatment for
at-risk patients was associated with a lessened risk for treatment failure with an odds ratio
of 0.327. Furthermore, using an α of 0.95, and a power of 80%, 49 patients in each group is
needed, meaning a randomized sample of 98 patients. As the algorithm developed for this
project identifies approximately 50% of patients, this means a total sample of 196 patients.
Based on an attrition rate of 20%, the total number of patients needed are 235. To obtain
slightly broader margins for attrition, we will include a total number of 240 participants.
Recruitment Participants will be recruited primarily through advertisements in newspapers and
on the Internet (including social media). Junior and senior high schools will also be
contacted to inform about the study. User organizations will be involved in informing about
the study and recruiting participants.
Blinding/masking For at-risk-participants allocated to adapted treatment, therapists cannot
be blind to allocation. However, participants are not informed that they are classified as at
risk for non-response. For all other participants, meaning participants classified as
on-track as well as participants classified as at-risk randomly allocated to the IPDT as
usual-arm, both participant and therapist will be blind to classification. All of the outcome
measures are self-rating scales, rendering blinding of assessors irrelevant.
Data management Data management in the study will follow the established procedures for
studies on Internet-based treatments conducted by the research groups of Per Carlbring at
Stockholm University and Gerhard Andersson at Linköping University. These procedures have
been used in a vast amount of studies conducted over several years. All individuals
participating in the project will be assigned a unique study code, used throughout the
project for communication via the Internet. All correspondence with the participants will be
made using a secure communication system. Importantly, no communication with the participant
will be made using standard email. All communication and data collected through
Internet-based self-report measures will only be associated with the unique identifier, and
no personal information. While the project is on-going all data (communication and data from
self-report measures) will be stored in an encrypted database, only accessible by the primary
study administrators. Personal information will be stored in a fireproof safe that only the
study administrators can access. The key that links participants to their unique study code
will be stored in a separate fireproof safe fulfilling the regulations concerning safe
storage of data. The data management procedures adhere to the General Data Protection
Regulation (GDPR).
Statistical methods Based on data from the large non-inferiority trial conducted in the
present research project (Mechler et al., 2022), an algorithm has been developed to identify
participants at risk of non-response or deterioration. Based on the data from Mechler et al.,
2022 and using the F1-score as precision measure (Sasaki, 2007), this algorithm made
predictions of non-response at treatment week 3 that could be trusted to 59% (i.e. a positive
prediction value of 0.59) and with specificity of 80%. This algorithm is based on linear
mixed models and uses data from weekly measurements of QIDS-A17-SR as well as baseline
ratings of the Personality Inventory for the Diagnostic and Statistical Manual of mental
disorders 5 Brief Form (PID 5-BF). Using stratified 5-fold cross validation, different mixed
models were trained on data from Mechler et al., 2022 using Bayesian estimation methods with
a Markov chain Monte Carlo (MCMC) algorithm (Dimitris, 2016). The best performing model for
finding at-risk patients (evaluated by the F1 measure) had a logarithmic change term for
modelling the weekly measurements of QIDS-A17-SR and baseline ratings of PID 5-BF as
covariate. Using parameters from this model, Bayesian estimation with MCMC will be used in
the same way as in the training step to make predictions of QIDS-A17-SR values for future
time points in the present study. At-risk patients will be patients predicted by the model
not to meet the two treatment response criteria defined by Hiller et al. (2012) at the last
treatment session.
Primary outcomes will be assessed using odds ratios. Secondary outcomes exploring
trajectories of change will use rates-of-change estimates based on linear mixed models.
Differences in efficacy between conditions will be investigated by modelling interaction
effects of group and time. These methods have been recommended for RCTs investigating
internet interventions (Hesser, 2015). One important advantage is their ability to handle
missing data, using full information maximum likelihood estimation (Gueorguieva & Krystal,
2004). The process of change will be examined thoroughly by employing longitudinal mediation
in a structural equation modelling (SEM) framework. In case mediators are found, causality
will be tested by including the mediator as lagged time-varying covariate in the model, i.e.
testing if change in an outcome variable at a certain time-point can be predicted by change
in a mediating variable at a previous time-point.
Dissemination of Results and Publication Policy The primary outcome paper will present
outcome data in a journal with open access publication. No outcome data will be published or
presented before data collection is completed. The results will also be disseminated in
popular science form through different media, partly with help of the user representatives
from Suicide Zero.
Ethics and safety considerations Approval of the Swedish Ethical Review Authority was decided
on 13th November, 2023. Participants give informed consent prior to screening. Correspondence
takes place in a closed system accessible with double authentication, data encrypted, and
stored in accordance with Swedish law. Data is analysed and reported at group-level. Thorough
inclusion interviews ensure that psychiatric problems making the treatment unsuitable or
indication of suicidality are ruled out and the young person will be referred to relevant
care. An experienced psychiatrist is participating in the study, who partakes in assessing
suitability versus unsuitability, and referring adolescents who need more specialized
treatment. Participants who express increased suicidality or severe deterioration will be
called up by their therapist or by the principal investigator and risk of suicidality or
self-harm will be assessed. If a participant is considered as suicidal, the psychiatrist will
make a second assessment and help the young person to relevant care. If participants under 18
express increased suicidal ideation, deteriorates severely or do not respond when contacted,
legal guardian(s) will be contacted. All participants will be advised to inform their legal
guardian(s) about their participation in the trial. All adverse events will be recorded and
reported in the study. Those events judged as serious adverse events (such as suicide risk,
substance misuse, or on-going maltreatment or sexual abuse) will lead to actions to ensure
the safety of the patient, and that he/she receives adequate help. Participants are informed
that they may withdraw from the study for any reason at any time.
