The Activate study is a parallel, single blind, superiority randomised controlled trial. Participants will be randomly assigned to receive either Activate (
n = 100) or treatment as usual (TAU;
n = 100), stratified by treatment modality (RR and OST). Treatment as usual is the comparator group, as it is clinically important to determine whether Activate adds any benefit in terms of improved depression symptomatology and reduced dependence symptoms, beyond that gained from usual care (i.e. RR or OST). Separate randomisation schedules will be used for the two treatment modalities. To reduce the risk of bias, minimisation, a dynamic random allocation technique, will be completed by someone independent of the research team using Minim-Py [
48]. Gender and depression severity have been identified as significant prognostic factors and minimisation will ensure classification of participants with respect to these variables. Depression severity will be categorised according to BDI-II score, as mild (14–19), moderate (20–28) or severe (29–63) [
49]. Minimisation has been shown to have both theoretical and practical validity, in particular it is considered an effective randomisation tool in clinical trials of small to moderate sample size (approximately,
N = 200–400) with multiple prognostic factors to be considered [
50‐
52].
The National Health and Medical Research Council of Australia (NHMRC) provided a project grant (#10444625) enabling the Activate study to be conducted. The funding period was initially February 2013 to December 2015, but was extended to December 2016 to accommodate extension of the baseline recruitment phase. Ethics approval was obtained from the University of New South Wales Human Research Ethics Committee (HREC) (Ref No: HC13155), and the Northern Sydney Local Health District HREC (Ref No: HREC/12/HAWKE /404). A model of the information and consent form used is available as supplementary material (Additional file
1). The study has been prospectively registered in the Australian and New Zealand Clinical Trials Registry (
ACTRN12613000876796, 7/08/13). Any changes to the trial protocol which may impact the conduct of the study, the benefit to the patient or patient safety, will require a formal amendment to the protocol. Approval for such amendments will be sought from the HRECs and the trial registry will be updated. See Table
1 for the WHO Trial Registration Data Set. Additional information regarding groups overseeing the trial, insurance coverage, and authorship guidelines can be found in the supplementary material (Additional file
1).
Table 1
Trial registration data set as recommended by the World Health Organization (WHO)
Primary registry and trial identifying number | |
Date of registration in primary registry | 7 August, 2013 |
Secondary identifying numbers | Universal Trial Number U1111-1142-2213 |
Source(s) of monetary or material support | National Health and Medical Research Council |
Primary sponsor | National Drug & Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052 |
Contact for public queries | Joanne Ross (j.ross@unsw.edu.au) |
Contact for scientific queries | Joanne Ross National Drug & Alcohol Research Centre, UNSW, Sydney, Australia |
Public title | Treatment for depression among people with substance use disorder: The Activate Study |
Scientific title | The efficacy of behavioural activation therapy for co-occurring depression and substance use disorder: The Activate Study |
Countries of recruitment | Australia |
Health condition(s) or problem(s) studied | Depression and Substance Use Disorder |
Intervention(s) | The intervention is Behavioral Activation Treatment for Depression (BATD-R), modified for use in outpatient and in-patient drug and alcohol treatment settings (Activate). Comparator: Treatment as usual i.e. Residential Rehabilitation (RR) or Opioid Substitution Treatment (OST). |
Key inclusion and exclusion criteria | Inclusion criteria: a) 18 years of age or older b) Literate in English c) Willing to give locator information d) Entered RR within the last month or in OST for at least 3 months e) Endorse CIDI 3.0 depression screening criteria f) Score at least in the mild range on PHQ-9 g) Substance use in the month prior to interview Exclusion criteria: a) Active suicidality b) Active psychosis c) Organic or traumatic brain injury d) Not living in the greater Sydney metropolitan area e) Not living in the community in the month prior to baseline |
Study type | Interventional. Allocation: randomised; intervention model: parallel assignment; Masking: the research officers assessing outcomes are blind to the allocation Primary purpose: Treatment |
Date of first enrolment | 12/08/2013 |
Target sample size | 200 |
Recruitment status | Recruitment completed. Analysis ongoing. |
Primary outcome(s) | 1) Depression Severity - Beck Depression Inventory (BDI-II) score - Composite International Diagnostic Interview 3.0 (CIDI) assessment of Major Depression. 2) Substance Use Disorder - CIDI assessment of substance use disorder - Severity of dependence scale (SDS) |
Key secondary outcomes | 1) Treatment feasibility as assessed by treatment retention and client satisfaction (assessed using the Client Satisfaction Questionnaire on completion of the Activate intervention) 2) Factors that influence the efficacy of the modified BATD-R (Activate) including client and treatment characteristics (assessed at baseline, 3 and 12 months). |
Sample size calculation
Power analysis on the primary outcome variables (i.e., severity of dependence and depressive symptoms) was conducted using Power Analysis and Sample Size software [
53]. Based on previous research, including the longitudinal study of treatment outcomes for heroin dependence (ATOS; [
20]), an exchangeable working correlation matrix and a within-subject correlation of ρ
1 = .60 for dependence and ρ
1 = .023 for depression was assumed. The proposed final sample size of 160 will allow for the detection of clinically meaningful differences between the treatment and control groups. Specifically, it will allow for the detection of a time-averaged difference of 3 in severity of substance dependence with a standard deviation of 5 (β = 99 % power;
α = 0.05); a 15 % difference in the prevalence of substance dependence (β = 96 % power;
α = 0.05); a difference of 5 in BDI-II scores with a standard deviation of 15 (β = 81 % power;
α = 0.05); and a 15 % difference in the prevalence of major depression (β = 93 % power;
α = 0.05). To allow for an expected attrition rate of 20 %, the initial sample will be 200, with the aim of recruiting 50 % of participants from RR and 50 % from OST.
Participants will be 18 years of age or older, literate in English, willing to give locator information, and must have been in RR for at least 1 week or OST for at least 3 months. RR clients must have used a substance (i.e., alcohol, methamphetamines, cannabis, cocaine, hallucinogens, illicit benzodiazepines, heroin or other opiates/opioids) at least four times in the month prior to detoxing, and OST clients must have used a substance at least four times in the past month. If alcohol is the only substance used, individuals need to have consumed four or more standard drinks on at least 4 days in the month before detoxing/past month. The depression screening criteria from the Composite International Diagnostic Interview 3.0 (CIDI; [
54,
55]) must be endorsed, indicating that the individual has experienced symptoms of depression that persisted for 2 weeks or longer in the month before detoxing/past month, and these symptoms must be ongoing. Depression symptom severity will be assessed using the Patient Health Questionnaire (PHQ-9; [
56]), with a score in the mild to severe range (i.e., 5–27) required to be eligible for the study.
Active suicidality, psychosis and organic or traumatic brain injury will exclude an individual from entering the study. Suicidality is assessed by the PHQ-9 during the screening interview. Participants are asked “in the past 2 weeks/2-weeks before detox, have you been bothered by thoughts that you would be better off dead.” If participants indicate that they have been bothered by these thoughts, the research officer then probes further, using questions taken from the Suicide Assessment Kit screener [
57], to determine whether these thoughts are ongoing, how long they have been having the thoughts, how intense they are, how likely it is that they will act on these thoughts in the near future, whether they have ever attempted suicide previously, and if so, how recently. Individuals who have attempted suicide in the past 6 months and for whom nothing has changed (i.e., they have received no intervention, or nothing has changed in their circumstances to reduce their risk), will be excluded from the study, and given a referral for appropriate support. If the thoughts are intense or the participant deems it likely that they will act on them in the near future, they are asked about any current plans and prior attempts, and are referred to an appropriate staff member at the treatment service for ongoing support and management.
Suicidality is assessed further as part of the baseline interview. The BDI-II and CIDI 3.0 both ask questions about suicidal thoughts, with the CIDI also asking about plans and attempts [
49,
55]. Additional questions about the lifetime number of suicide attempts and recency of the last attempt are also asked. In situations where suicidality is indicated, the research officer uses the additional probing questions described above to assess their current risk, and to determine whether there is a need for exclusion from the study and referral for additional support. It is possible for a person with a current plan and thoughts of suicide to be recruited to the study provided the risk is not deemed imminent, and the treatment service is made aware of the suicidal thoughts and plan.
As part of the screening questionnaire, potential participants are asked whether they have ever been diagnosed with bipolar, mania, or schizophrenia. If the response is yes, (or if the individual reports being prescribed antipsychotics during the baseline interview), the project psychologist will meet briefly with them and ask them whether they ever see or hear things that other people cannot see or hear, whether the hallucinations are believed to be drug induced, whether the hallucinations are current, and how these are managed. These individuals are also asked about having unusual thoughts or beliefs. The psychologist then makes a clinical decision about their eligibility for the study. Self-report of having received a diagnosis of traumatic brain injury, as ascertained during the screening interview, is also a reason for exclusion.
Exclusion from the study in all of the above cases is based on the individual’s inability to effectively engage with, and thus benefit from, the type of intervention offered. Decisions to exclude on the basis of suicidality, psychosis or traumatic brain injury will all be made in consultation with the project coordinator and/or a project psychologist prior to randomisation. Alternate referral for treatment will be provided where necessary. Additionally, for reasons of feasibility in providing the Activate intervention and contacting participants for follow-up, clients will be excluded if they do not live in the Greater Sydney Metropolitan, Central Coast or Hunter New England regions. To ensure that participants have been at liberty to use substances in the month prior to detox or past month, individuals not living in the community (e.g., incarcerated) during that period will be excluded.