Clinical trial NCT04140838: Cost-utility and Physiological Effects of ACT and BATD in Patients With Chronic Pain and Depression
Official title: Cost-utility and Physiological Effects of Acceptance and Commitment Therapy and Behavior Activation in Patients With Chronic Pain and Comorbid Major Depression (IMPACT Project)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Randomized Controlled Trial
Lead sponsor: Fundació Sant Joan de Déu
Sponsor class: OTHER
Collaborators: name: Carlos III Health Institute
First posted: 2019-10-28
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-blind, parallel-group, randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Objectives: (1) To analyze the effectiveness of adding a group-based form of Acceptance and Commitment Therapy (ACT) or a behavioural activation program for depression (TACD) to the treatment as usual (TAU) for patients diagnosed of chronic pain and comorbid mild-moderate major depression; (2) To examine the cost-utility of these psychological treatments from healthcare and societal perspectives; (3) To measure a set of biomarkers alongside the RCT in order to know the physiological underpinnings of these psychological therapies and to identify potential predictors of treatment response.

Methodology: 12-month multisite, randomised, controlled trial (RCT) Centres: Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat) and Hospital del Mar (Barcelona).

Participants. 225 adult patients with chronic pain that meet the diagnostic criteria for mild-moderate major depression will be randomly assigned to one of the three study arms: TAU + ACT vs. TAU + TACD vs. TAU.

Primary outcome: Quality of life. Secondary outcomes: pain intensity, depression severity, anxiety symptoms, pain catastrophising, and pain acceptance. Costs to the healthcare system and to society and quality adjusted life years (QALYs). In addition, the empirically validated app Multicenter Pain Monitor® will be used to monitor participants alongside the treatments (ecological momentary assessment). Biomarkers: hair cortisol and cortisone, corticosteroid-binding globulin (CBG), ACTH and cortisol in plasma, and genotyping of 5 polymorphisms in the FKBP5 gene involved in the regulation of the hypothalamic-pituitary-adrenal axis activity, cytokines, Th1: IL-6, IL-8, TNF-α; cytokines Th2: IL-10 + hsCRP test, and vitamin D levels. Main statistical analyses: Intention-to-Treat analyses that will include all participants who undergo random allocation, using multiple imputation to replace missing values. Linear mixed-effects models will be performed using Restricted Maximum Likelihood to estimate the parameters. Calculation of between-groups effect sizes using Cohen's d and of the number-needed-to-treat. Economic evaluation: cost-utility ratios evaluated by applying bootstrapping techniques, acceptability curves, and sensitivity analyses.

Detailed description: The IMPACT Project's main objective is to determine the effectiveness of adding to the standard care of patients with chronic pain and mild to moderate major depression a group programme based on ACT or a group programme based on BATD and analyse the cost-utility of these psychological treatments from a health and social perspective. Likewise, both in chronic pain and in other usually associated psychiatric diseases, there is a ubiquitous lack of knowledge about what specific psychological and physiological mechanisms are modified by these third generation psychotherapies and how they relate to the observed clinical results. The potential predictors of response to these treatments are also unknown. In chronic musculoskeletal pain where central sensitization plays an important role, alterations have been found in different markers associated with an increased experience of pain. Some of these alterations in markers (e.g. high levels of pro-inflammatory cytokines) would also appear to be shared with other psychiatric diseases (major depression), a fact that would suggest a possible common mechanism involved in the etiopathogenesis of these diseases. Third generation psychotherapies have proven effective for pain management and regulation of the immune response. The IMPACT Multicentre Project (Improving Pain and Depression with ACT and BATD) will significantly expand the limited knowledge available about how ACT and BATD therapies exert their effects on relevant clinical improvement variables and will try to identify response predictive factors to these treatments.

Eligibility criteria: Inclusion Criteria:

Patients who have been visited in the last 3 years in the participating centres and who have been given a diagnosis of chronic non-cancer musculoskeletal pain. In telephone screening, it will be evaluated whether the current pain intensity is at least moderate and PHQ-9 will be administered to confirm the presence of mild to moderate active depression.

1. Patients between 18 and 70 years of age.
2. Diagnosis of chronic pain (≥ 3 months) according to medical history (current pain ≥ 4 out of 10)
3. Diagnosis of mild to moderate depression according to PHQ-9 (score between 5 and 19).
4. Understanding of Spanish.
5. Access to a Smartphone (with Android operating system).
6. Written informed consent.

Exclusion Criteria:

1. Presence of cognitive impairment according to MMSE (≤ 24 out of 30).
2. Previous (last year) or current psychological treatment.
3. Presence of severe mental disorder (e.g. psychotic disorder) related to substance dependence/abuse or another disease that affects the CNS (organic brain pathology or head trauma of any severity).
4. Presence of serious, uncontrolled or degenerative medical disease that may interfere with affective symptoms.
5. Risk of suicide (Item 9 score of PHQ-9 ≥ 2).
6. Patients involved in legal proceedings with employers in relation to their illness.
7. Patients with scheduled surgical intervention or other interventions.
8. Inability to attend group treatment sessions.

Additional exclusion criteria for the study of biomarkers (50% of subjects in each branch):

1. Cold/infection symptoms on the day of blood collection.
2. Needle phobia.
3. BMI \> 36 kg/m2 or weight \> 110 kg
4. Consumption \> 8 units of caffeine per day (maximum 1 drink with caffeine on the day of testing).
5. Smoker \> 5 cigarettes a day.
6. Being pregnant or breastfeeding

Primary outcomes:
measure: Aggregate score of the Physical Function, Body Pain and Vitality subscales of the SF-36
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Numerical pain scale
timeFrame: Through study completion, an average of 1 year
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Through study completion, an average of 1 year.
measure: Pain Catastrophising Scale (PCS)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
measure: Psychological Inflexibility in Pain Scale (PIPS)
timeFrame: Through study completion, an average of 1 year
measure: EuroQoL (EQ-5D-5L)
timeFrame: Through study completion, an average of 1 year
measure: Behavioral Activation for Depression Scale (BADS) - short-form
timeFrame: Through study completion, an average of 1 year
measure: Credibility/Expectancy questionnaire (CEQ)
timeFrame: Baseline
measure: Client Service Receipt Inventory (CSRI)
timeFrame: Through study completion, an average of 1 year
measure: Adverse effects of treatments
timeFrame: Through study completion, an average of 1 year
measure: The Pain Monitor® app
timeFrame: Through study completion, an average of 1 year
measure: Socio-demographic questionnaire
timeFrame: Baseline
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline
Locations:
city: Sant Boi De Llobregat
country: Spain
facility: Parc Sanitari Sant Joan de Déu (PSSJD)
state: Barcelona
city: Barcelona
country: Spain
facility: Parc de Salut Mar
Study officials:
affiliation: Fundació Sant Joan de Déu
name: Juan V. Luciano, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanabria-Mazo JP, Forero CG, Cristobal-Narvaez P, Suso-Ribera C, Garcia-Palacios A, Colomer-Carbonell A, Perez-Aranda A, Andres-Rodriguez L, McCracken LM, D'Amico F, Estivill-Rodriguez P, Carreras-Marcos B, Montes-Perez A, Comps-Vicente O, Esteve M, Grasa M, Rosa A, Cuesta-Vargas AI, Maes M, Borras X, Edo S, Sanz A, Feliu-Soler A, Castano-Asins JR, Luciano JV. Efficacy, cost-utility and physiological effects of Acceptance and Commitment Therapy (ACT) and Behavioural Activation Treatment for Depression (BATD) in patients with chronic low back pain and depression: study protocol of a randomised, controlled trial including mobile-technology-based ecological momentary assessment (IMPACT study). BMJ Open. 2020 Jul 23;10(7):e038107. doi: 10.1136/bmjopen-2020-038107.
citation: Sanabria-Mazo JP, Colomer-Carbonell A, Borras X, Castano-Asins JR, McCracken LM, Montero-Marin J, Perez-Aranda A, Edo S, Sanz A, Feliu-Soler A, Luciano JV. Efficacy of Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A Randomized Controlled Trial (IMPACT Study). J Pain. 2023 Aug;24(8):1522-1540. doi: 10.1016/j.jpain.2023.04.008. Epub 2023 Apr 25.