Multiple Sclerosis (MS) - Relapsing-remittingMS-PSYNCT07273604
Psychological Interventions for Multiple Sclerosis: Effects on Anxiety, Depression, and Cognition.
A study testing Cognitive Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) in people with Multiple Sclerosis (MS) - Relapsing-remitting and Anxiety, run by Moisés Bermúdez Hernández at 1 site in Spain.
Trial summary
This study evaluated the efficacy of two structured psychological interventions in individuals with relapsing-remitting multiple sclerosis (RRMS). The main objective was to evaluate whether Group-Based Cognitive-Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) improved emotional well-being and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis (MS) - Relapsing-remitting, Anxiety, Depression
- What is being tested?
- Cognitive Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteSpain
- Study dates
- 1 Feb 2015to 1 Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of relapsing-remitting multiple sclerosis according to standard clinical criteria.
- Expanded Disability Status Scale (EDSS) score between 0 and 3.5.
- Mild to moderate cognitive impairment defined as: up to two BRB-N subtests with scores < -2 SD.
- Presence of anxiety or depressive symptoms defined as:
- HADS: score > 8 on one or both subscales, and/or
- BDI-II: score > 8.
- Stable disease-modifying treatment for ≥ 3 months.
- Ability to provide written informed consent.
Who cannot join
- Progressive forms of multiple sclerosis (SPMS or PPMS).
- Severe cognitive impairment preventing participation in psychological sessions.
- Active psychiatric or neurological disorders unrelated to MS.
- Participation in another psychological or pharmacological intervention study.
- Recent initiation or modification of disease-modifying treatment (< 3 months).
- Substance abuse or dependence within the past year.
- Inability to provide informed consent.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Faculty of Psychology, University of La Laguna Department of Clinical Psychology, Psychobiology and Methodology of Behavioral Sciences Campus de Guajara, Calle Heraclio Sánchez, s/n 38200 San Cristóbal de La Laguna, Santa Cruz de Tenerife Spain
San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38200
About this study
Official title: Psychological Intervention in Multiple Sclerosis: Efficacy in the Treatment of Anxiety-depressive Symptoms and Cognitive Impairment.
This study evaluated the efficacy of two structured psychological interventions in individuals with relapsing-remitting multiple sclerosis (RRMS). The main objective was to evaluate whether Group-Based Cognitive-Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) improved emotional well-being and objective cognitive functioning compared with Standard Care (SC).
A total of 153 individuals with RRMS were assessed for eligibility, of whom 148 were randomized to one of three study conditions: Group-Based CBT, PRT, or SC (waiting-list control). Participants were allocated using a simple computer-generated randomization sequence with a 1:1:1 allocation ratio.
Read more
Both active interventions were delivered in small groups over 12 weekly sessions. CBT and PRT shared a common therapeutic framework comprising psychoeducation, mindfulness, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10.
Assessments were conducted at baseline and immediately after completion of the 12-week intervention period using standardized psychological and neuropsychological measures. The study evaluated treatment effects across complementary domains of emotional functioning and objective cognitive performance.
Read the detailed description
A total of 153 individuals with RRMS were assessed for eligibility at the Multiple Sclerosis Unit of Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Tenerife, Spain. Five individuals were excluded (three declined to participate and two did not meet the inclusion criteria), resulting in a final randomized sample of 148 participants.
Participants were randomly allocated to one of three parallel study conditions: Group-Based Cognitive-Behavioral Therapy (CBT), Psychophysiological Regulation Therapy (PRT; active comparator), or Standard Care (SC; waiting-list control). Allocation was performed using a simple computer-generated randomization sequence created in IBM SPSS Statistics with a 1:1:1 allocation ratio. No blocking or stratification was used. The randomization sequence was generated by an independent member of the research team who was not involved in participant recruitment, outcome assessment, or treatment delivery. Following completion of baseline assessments and verification of eligibility, an anonymized participant list was provided to the independent methodologist, who generated the allocation sequence. Participants were subsequently assigned to the study conditions according to this predefined sequence.
Participants allocated to the CBT and PRT conditions completed twelve weekly group sessions delivered over a 12-week period, followed by one individual follow-up session. Both active interventions shared a common therapeutic framework comprising psychoeducation about multiple sclerosis and stress management, mindfulness training, psychophysiological regulation strategies, and homework assignments. This common therapeutic framework was delivered in sessions lasting approximately 60 minutes.
The PRT intervention comprised the common therapeutic framework throughout the 12-week program, with sessions lasting approximately 60 minutes. The CBT intervention incorporated the same common therapeutic framework but additionally included cognitive-behavioral components during sessions 4-10, comprising behavioral activation, thought stopping, self-instruction training, cognitive restructuring, problem-solving strategies, and social skills training. Sessions incorporating these additional CBT-specific components were extended to approximately 90 minutes, including a 10-minute break.
Participants assigned to Standard Care continued receiving their usual neurological care and did not receive any additional psychological intervention during the trial. All participants continued receiving their usual neurological care, including disease-modifying treatment and routine clinical follow-up, throughout the study period.
Assessments were conducted at baseline and immediately after completion of the 12-week intervention period. Psychological and emotional functioning was assessed using standardized self-report measures, and objective cognitive functioning was evaluated using standardized neuropsychological measures. Alternate forms of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) were used at baseline and post-treatment to minimize practice effects.
Outcome assessors remained blinded to treatment allocation throughout the trial, although participants and therapists could not be blinded because of the nature of the psychological interventions. Clinical stability, relapse occurrence, changes in disease-modifying treatment, and the emergence of additional neurological or psychiatric conditions were monitored throughout the study. No intervention-related adverse events or unintended effects were reported.
- Conditions
- Multiple Sclerosis (MS) - Relapsing-remitting, Anxiety, Depression, Cognitive Impairment, Emotional Well-being, Cognitive Behavior Therapy
- Being tested
- Cognitive Behavioral Therapy (CBT), Psychophysiological Regulation Therapy (PRT)
- Keywords
- Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Cognitive Behavioral Therapy, Psychophysiological Regulation Therapy, Anxiety, Depression, Cognitive Impairment, Emotional Well-being, Quality of Life, Fatigue, Randomized Controlled Trial, Psychological Intervention
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Anxiety Disorders, Depression, Cognitive Dysfunction, Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral Therapy (CBT)Behavioural
A structured 12-week group-based cognitive-behavioral intervention including psychoeducation, mindfulness training, behavioral activation, cognitive restructuring, self-instruction training, and social skills development. Designed to improve coping, reduce anxiety-depressive symptoms, and enhance cognitive and emotional functioning.
Psychophysiological Regulation Therapy (PRT)Behavioural
A structured 12-week group-based intervention emphasizing psychophysiological self-regulation through psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises to reduce emotional distress and promote physiological balance.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Experimental | Participants receive a structured 12-week cognitive-behavioral group intervention designed to improve stress coping and reduce anxiety-depressive symptoms. The program includes psychoeducation, mindfulness, behavioral activation, cognitive restructuring, self-instruction training, and social skills development.
Intervention: Behavioral: Cognitive Behavioral Therapy Receives: Behavioral: Cognitive Behavioral Therapy (CBT) |
| Psychophysiological Regulation Therapy (PRT) | Experimental | Participants receive a structured 12-week group intervention emphasizing psychophysiological self-regulation. The program includes psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises aimed at reducing emotional distress and enhancing self-regulation. Receives: Behavioral: Psychophysiological Regulation Therapy (PRT) |
| Standard Care (SC) | No intervention | Participants in the control group remain on a waiting list and receive standard medical care provided by the Multiple Sclerosis Unit during the study period. After study completion, they are offered participation in one of the active interventions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Severity Scale (FSS) - Total Score
Description: Change in fatigue severity measured with the Fatigue Severity Scale (FSS; Krupp et al., 1989).
Scale range: 9-63 points (9 items scored 1-7). Interpretation: Higher scores indicate greater fatigue severity.
Measured: Baseline and 12 weeks.
Multiple Sclerosis Quality of Life-54 (MSQoL-54) - Total and Subscale Scores
Description: Change in quality of life measured with the Multiple Sclerosis Quality of Life-54 (MSQoL-54; Vickrey, Hays, Harooni, Myers \& Ellison, 1995), including physical and mental health composite scores and individual subscales.
Scale range: 0-100 points. Interpretation: Higher scores indicate better quality of life.
Measured: Baseline and 12 weeks.
Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) - Total Score
Description: Change in perceived cognitive functioning measured with the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ; Benedict et al., 2003).
Scale range: 0-60 points. Interpretation: Higher scores indicate greater perceived cognitive impairment.
Measured: Baseline and 12 weeks.
Verbal Selective Reminding Test (SRT) - Total Recall Score
Change in verbal learning and memory performance measured with the Verbal Selective Reminding Test (SRT), part of the BRB-N (Rao, 1990). (Scale range 0-72). Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
10/36 Spatial Recall Test (SPART) - Total Recall Score
Description: Change in visuospatial learning and memory measured with the 10/36 Spatial Recall Test (SPART), part of the BRB-N (Rao, 1990).
Scale range: 0-36. Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
Paced Auditory Serial Addition Test (PASAT) - 3-Second Version
Description: Change in complex attention and working memory measured with the PASAT (3-second version), part of the BRB-N (Rao, 1990).
Scale range: 0-60 correct responses. Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
Symbol Digit Modalities Test (SDMT) - Oral Version
Description: Change in attention and processing speed measured with the Symbol Digit Modalities Test (SDMT), part of the BRB-N (Rao, 1990).
Scale range: 0-110 correct responses. Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
Controlled Oral Word Association Test (COWAT) - Semantic Fluency ("Animals" Category)
Description: Change in semantic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Semantic Fluency subtest (animals category).
Scale range: Number of correct animals named in 60 seconds (typically 0-40). Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
Controlled Oral Word Association Test (COWAT) - Phonemic Fluency (F-A-S Letters)
Description: Change in phonemic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Phonemic Fluency subtest (letters F, A, and S).
Scale range: Total number of correct words generated across the three letters in 60 seconds each (typically 0-60).
Interpretation: Higher scores indicate better performance.
Measured: Baseline and 12 weeks.
Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A)
Description: Change in anxiety symptoms measured with the Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A; Zigmond \& Snaith, 1983).
Scale range: 0-21 points. Interpretation: Higher scores indicate greater anxiety severity.
Measured: Baseline and 12 weeks.
Beck Depression Inventory-II (BDI-II) - Total Score
Description: Change in depressive symptoms measured with the Beck Depression Inventory-II (BDI-II; Beck et al., 1996).
Scale range: 0-63 points. Interpretation: Higher scores indicate greater depressive severity.
Measured: Baseline and 12 weeks.
Inventario de Situaciones y Respuestas de Ansiedad (ISRA) - Total Score
Description: Change in cognitive, physiological, and motor anxiety responses measured with the Inventario de Situaciones y Respuestas de Ansiedad (ISRA; Miguel-Tobal \& Cano-Vindel, 1994).
Scale range: 0-100+ (higher scores = greater anxiety response). Interpretation: Higher scores indicate greater anxiety reactivity.
Measured: Baseline and 12 weeks.
Secondary outcomes (8)
Recent Life Changes Questionnaire (RLCQ) - Total Score
Description: Change in perceived stress measured with the Recent Life Changes Questionnaire (RLCQ; Holmes \& Rahe, 1967; Spanish adaptation: González \& Morera, 1983).
Scale range: 0 to 100+ life change units (LCUs), depending on the number and weight of events endorsed.
Interpretation: Higher scores indicate greater perceived stress and higher adjustment demand.
Measured: Baseline and 12 weeks.
Symptom Checklist-90-Revised (SCL-90-R) - Global Severity Index (GSI)
Description: Change in general psychopathological symptoms measured with the Symptom Checklist-90-Revised (SCL-90-R; Derogatis, 1994), using the Global Severity Index (GSI).
Scale range: 0-4 (mean item score across 90 items rated 0 to 4). Interpretation: Higher scores indicate greater psychopathological symptom severity.
Measured: Baseline and 12 weeks.
Cognitive Triad Inventory (CTI) - Total Score
Description: Change in depressive cognitive schemas measured with the Cognitive Triad Inventory (CTI; Beckham et al., 1986).
Scale range: 36-252 points (36 items scored 1-7). Interpretation: Higher scores indicate more negative/depressive cognitive schemas about self, world, and future.
Measured: Baseline and 12 weeks.
Intolerance of Uncertainty Scale (IUS) - Total Score
Description: Change in intolerance of uncertainty measured with the Intolerance of Uncertainty Scale (IUS; Freeston et al., 1994).
Scale range: 27-135 points (27 items scored 1-5). Interpretation: Higher scores indicate greater intolerance of uncertainty.
Measured: Baseline and 12 weeks.
Social Support Questionnaire (SSQ-6) - Total Score
Description: Change in perceived social support measured with the Social Support Questionnaire (SSQ; Sarason et al., 1983).
Scale range: Typically 0-9 for the number of supports (SSQ-6) and 1-6 for satisfaction (SSQ-S), depending on the scoring method used.
Interpretation: Higher scores indicate greater perceived social support (more available supports and/or higher satisfaction).
Measured: Baseline and 12 weeks.
Pittsburgh Sleep Quality Index (PSQI) - Total Score
Description: Change in sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI).
Scale range: 0-21 points. Interpretation: Higher scores indicate worse sleep quality.
Measured: Baseline and 12 weeks.
MRI Lesion Activity and Lesion Load
Change in brain lesion activity (number of new/enlarging T2 lesions and gadolinium-enhancing lesions) and total lesion load (total T2 lesion volume) obtained from routine clinical magnetic resonance imaging (MRI) scans.
Measured: Baseline and 12 weeks.
Duke-UNC Functional Social Support Questionnaire (DUFSS) - Total Score
Description: Change in functional social support measured with the Duke-UNC Functional Social Support Questionnaire (DUFSS; Broadhead et al., 1988; Spanish validation by Bellón et al., 1996).
Scale range: 5-55 points (11 items scored 1-5). Interpretation: Higher scores indicate greater functional social support.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2025
- Study start1 Feb 2015
- Primary completion1 Jan 2019
- Study completion1 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis (MS) - Relapsing-remittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study employed a three-arm randomized controlled parallel design. Participants were allocated to Group-Based Cognitive-Behavioral Therapy (CBT), Psychophysiological Regulation Therapy (PRT), or Standard Care (waiting-list control). Both active interventions were delivered over 12 weekly group sessions and shared a common therapeutic framework comprising psychoeducation about multiple sclerosis and stress management, mindfulness training, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10, including behavioral activation, thought stopping, self-instruction training, cognitive restructuring, problem-solving strategies, and social skills training. Assessments were conducted at baseline and immediately post-intervention.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Moisés Bermúdez Hernández
- Sponsor type
- University, hospital or other
- Collaborators
- University of La Laguna
- Responsible party
- Sponsor-investigator, Moisés Bermúdez Hernández, University of La Laguna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07273604
- Sponsor's protocol ID
- HUNSC_ULL_MS_PSY2015
- Other IDs
- PI-60/14
- Acronym
- MS-PSY
- Status last verified
- Sep 2026
- First submitted
- 19 Nov 2025
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) will be made available upon reasonable request to the corresponding author, Dr. Moisés Bermúdez Hernández (mbermudh@ull.edu.es), for academic and non-commercial research purposes. Data will be fully anonymized in compliance with institutional and ethical regulations and the European General Data Protection Regulation (GDPR).
Publications
Scandiffio J, Langer LK, Senthilnathan V, Feng G, Sureshkumar A, Bromberg M, Babineau J, Donkers SJ, Knox KB, Bruno T, Walker LAS, Bayley MT, Simpson R. Effects of psychological therapies in people with multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials. J Neurol. 2025 Aug 20;272(9):584. doi: 10.1007/s00415-025-13315-6.
PubMed 40833620Lucien A, Francis H, Wu W, Woldhuis T, Gandy M. The efficacy of cognitive behavioural therapy for depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2024 Nov;91:105858. doi: 10.1016/j.msard.2024.105858. Epub 2024 Sep 3.
PubMed 39276596Moss-Morris R, McCrone P, Yardley L, van Kessel K, Wills G, Dennison L. A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue. Behav Res Ther. 2012 Jun;50(6):415-21. doi: 10.1016/j.brat.2012.03.001. Epub 2012 Mar 13.
PubMed 22516321De Meo E, Portaccio E, Bonacchi R, Giovannoli J, Niccolai C, Amato MP. An update on the treatment and management of cognitive dysfunction in patients with multiple sclerosis. Expert Rev Neurother. 2025 Feb;25(2):227-243. doi: 10.1080/14737175.2025.2450788. Epub 2025 Jan 16.
PubMed 39801437Cuijpers P, Karyotaki E, Weitz E, Andersson G, Hollon SD, van Straten A. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis. J Affect Disord. 2014 Apr;159:118-26. doi: 10.1016/j.jad.2014.02.026. Epub 2014 Feb 24.
PubMed 24679399Amato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, Comi G. Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol. 2013 Jun;260(6):1452-68. doi: 10.1007/s00415-012-6678-0. Epub 2012 Nov 23.
PubMed 23180174
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychological Intervention in Multiple Sclerosis: Efficacy in the Treatment of Anxiety-depressive Symptoms and Cognitive Impairment.
- ClinicalTrials.gov ID
- NCT07273604
- Acronym / sponsor ID
- MS-PSY / HUNSC_ULL_MS_PSY2015
- Conditions
- Multiple Sclerosis (MS) - Relapsing-remitting, Anxiety, Depression, Cognitive Impairment, Emotional Well-being, Cognitive Behavior Therapy
- Keywords
- Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Cognitive Behavioral Therapy, Psychophysiological Regulation Therapy, Anxiety, Depression, Cognitive Impairment, Emotional Well-being
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Moisés Bermúdez HernándezUniversity, hospital or other
- Collaborators
- University of La Laguna
- Study start
- 1 Feb 2015 (actual)
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 1 Jan 2019 (actual)
- First posted
- 9 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the efficacy of two structured psychological interventions in individuals with relapsing-remitting multiple sclerosis (RRMS). The main objective was to evaluate whether Group-Based Cognitive-Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) improved emotional well-being and objective cognitive functioning compared with Standard Care (SC).
A total of 153 individuals with RRMS were assessed for eligibility, of whom 148 were randomized to one of three study conditions: Group-Based CBT, PRT, or SC (waiting-list control). Participants were allocated using a simple computer-generated randomization sequence with a 1:1:1 allocation ratio.
Both active interventions were delivered in small groups over 12 weekly sessions. CBT and PRT shared a common therapeutic framework comprising psychoeducation, mindfulness, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10.
Assessments were conducted at baseline and immediately after completion of the 12-week intervention period using standardized psychological and neuropsychological measures. The study evaluated treatment effects across complementary domains of emotional functioning and objective cognitive performance.
Detailed description
A total of 153 individuals with RRMS were assessed for eligibility at the Multiple Sclerosis Unit of Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Tenerife, Spain. Five individuals were excluded (three declined to participate and two did not meet the inclusion criteria), resulting in a final randomized sample of 148 participants.
Participants were randomly allocated to one of three parallel study conditions: Group-Based Cognitive-Behavioral Therapy (CBT), Psychophysiological Regulation Therapy (PRT; active comparator), or Standard Care (SC; waiting-list control). Allocation was performed using a simple computer-generated randomization sequence created in IBM SPSS Statistics with a 1:1:1 allocation ratio. No blocking or stratification was used. The randomization sequence was generated by an independent member of the research team who was not involved in participant recruitment, outcome assessment, or treatment delivery. Following completion of baseline assessments and verification of eligibility, an anonymized participant list was provided to the independent methodologist, who generated the allocation sequence. Participants were subsequently assigned to the study conditions according to this predefined sequence.
Participants allocated to the CBT and PRT conditions completed twelve weekly group sessions delivered over a 12-week period, followed by one individual follow-up session. Both active interventions shared a common therapeutic framework comprising psychoeducation about multiple sclerosis and stress management, mindfulness training, psychophysiological regulation strategies, and homework assignments. This common therapeutic framework was delivered in sessions lasting approximately 60 minutes.
The PRT intervention comprised the common therapeutic framework throughout the 12-week program, with sessions lasting approximately 60 minutes. The CBT intervention incorporated the same common therapeutic framework but additionally included cognitive-behavioral components during sessions 4-10, comprising behavioral activation, thought stopping, self-instruction training, cognitive restructuring, problem-solving strategies, and social skills training. Sessions incorporating these additional CBT-specific components were extended to approximately 90 minutes, including a 10-minute break.
Participants assigned to Standard Care continued receiving their usual neurological care and did not receive any additional psychological intervention during the trial. All participants continued receiving their usual neurological care, including disease-modifying treatment and routine clinical follow-up, throughout the study period.
Assessments were conducted at baseline and immediately after completion of the 12-week intervention period. Psychological and emotional functioning was assessed using standardized self-report measures, and objective cognitive functioning was evaluated using standardized neuropsychological measures. Alternate forms of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) were used at baseline and post-treatment to minimize practice effects.
Outcome assessors remained blinded to treatment allocation throughout the trial, although participants and therapists could not be blinded because of the nature of the psychological interventions. Clinical stability, relapse occurrence, changes in disease-modifying treatment, and the emergence of additional neurological or psychiatric conditions were monitored throughout the study. No intervention-related adverse events or unintended effects were reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- This study employed a three-arm randomized controlled parallel design. Participants were allocated to Group-Based Cognitive-Behavioral Therapy (CBT), Psychophysiological Regulation Therapy (PRT), or Standard Care (waiting-list control). Both active interventions were delivered over 12 weekly group sessions and shared a common therapeutic framework comprising psychoeducation about multiple sclerosis and stress management, mindfulness training, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10, including behavioral activation, thought stopping, self-instruction training, cognitive restructuring, problem-solving strategies, and social skills training. Assessments were conducted at baseline and immediately post-intervention.
| Arm | Type | Receives |
|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Experimental | Behavioral: Cognitive Behavioral Therapy (CBT)Participants receive a structured 12-week cognitive-behavioral group intervention designed to improve stress coping and reduce anxiety-depressive symptoms. The program includes psychoeducation, mindfulness, behavioral activation, cognitive restructuring, self-instruction training, and social skills development. Intervention: Behavioral: Cognitive Behavioral Therapy |
| Psychophysiological Regulation Therapy (PRT) | Experimental | Behavioral: Psychophysiological Regulation Therapy (PRT)Participants receive a structured 12-week group intervention emphasizing psychophysiological self-regulation. The program includes psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises aimed at reducing emotional distress and enhancing self-regulation. |
| Standard Care (SC) | No intervention | –Participants in the control group remain on a waiting list and receive standard medical care provided by the Multiple Sclerosis Unit during the study period. After study completion, they are offered participation in one of the active interventions. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of relapsing-remitting multiple sclerosis according to standard clinical criteria.
- Expanded Disability Status Scale (EDSS) score between 0 and 3.5.
- Mild to moderate cognitive impairment defined as: up to two BRB-N subtests with scores < -2 SD.
- Presence of anxiety or depressive symptoms defined as:
- HADS: score > 8 on one or both subscales, and/or
Key exclusion criteria (7 listed)
- Progressive forms of multiple sclerosis (SPMS or PPMS).
- Severe cognitive impairment preventing participation in psychological sessions.
- Active psychiatric or neurological disorders unrelated to MS.
- Participation in another psychological or pharmacological intervention study.
- Recent initiation or modification of disease-modifying treatment (< 3 months).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral Therapy (CBT)A structured 12-week group-based cognitive-behavioral intervention including psychoeducation, mindfulness training, behavioral activation, cognitive restructuring, self-instruction training, and social skills development. Designed to improve coping, reduce anxiety-depressive symptoms, and enhance cognitive and emotional functioning. | Behavioural | Cognitive Behavioral Therapy (CBT) |
| Psychophysiological Regulation Therapy (PRT)A structured 12-week group-based intervention emphasizing psychophysiological self-regulation through psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises to reduce emotional distress and promote physiological balance. | Behavioural | Psychophysiological Regulation Therapy (PRT) |
Primary outcome
Fatigue Severity Scale (FSS) - Total Score
Time frame: Baseline and 12 weeks.
Description: Change in fatigue severity measured with the Fatigue Severity Scale (FSS; Krupp et al., 1989). Scale range: 9-63 points (9 items scored 1-7). Interpretation: Higher scores indicate greater fatigue severity.
Multiple Sclerosis Quality of Life-54 (MSQoL-54) - Total and Subscale Scores
Time frame: Baseline and 12 weeks.
Description: Change in quality of life measured with the Multiple Sclerosis Quality of Life-54 (MSQoL-54; Vickrey, Hays, Harooni, Myers \& Ellison, 1995), including physical and mental health composite scores and individual subscales. Scale range: 0-100 points. Interpretation: Higher scores indicate better quality of life.
Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) - Total Score
Time frame: Baseline and 12 weeks.
Description: Change in perceived cognitive functioning measured with the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ; Benedict et al., 2003). Scale range: 0-60 points. Interpretation: Higher scores indicate greater perceived cognitive impairment.
Verbal Selective Reminding Test (SRT) - Total Recall Score
Time frame: Baseline and 12 weeks.
Change in verbal learning and memory performance measured with the Verbal Selective Reminding Test (SRT), part of the BRB-N (Rao, 1990). (Scale range 0-72). Interpretation: Higher scores indicate better performance.
10/36 Spatial Recall Test (SPART) - Total Recall Score
Time frame: Baseline and 12 weeks.
Description: Change in visuospatial learning and memory measured with the 10/36 Spatial Recall Test (SPART), part of the BRB-N (Rao, 1990). Scale range: 0-36. Interpretation: Higher scores indicate better performance.
Paced Auditory Serial Addition Test (PASAT) - 3-Second Version
Time frame: Baseline and 12 weeks.
Description: Change in complex attention and working memory measured with the PASAT (3-second version), part of the BRB-N (Rao, 1990). Scale range: 0-60 correct responses. Interpretation: Higher scores indicate better performance.
Symbol Digit Modalities Test (SDMT) - Oral Version
Time frame: Baseline and 12 weeks.
Description: Change in attention and processing speed measured with the Symbol Digit Modalities Test (SDMT), part of the BRB-N (Rao, 1990). Scale range: 0-110 correct responses. Interpretation: Higher scores indicate better performance.
Controlled Oral Word Association Test (COWAT) - Semantic Fluency ("Animals" Category)
Time frame: Baseline and 12 weeks.
Description: Change in semantic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Semantic Fluency subtest (animals category). Scale range: Number of correct animals named in 60 seconds (typically 0-40). Interpretation: Higher scores indicate better performance.
Controlled Oral Word Association Test (COWAT) - Phonemic Fluency (F-A-S Letters)
Time frame: Baseline and 12 weeks.
Description: Change in phonemic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Phonemic Fluency subtest (letters F, A, and S). Scale range: Total number of correct words generated across the three letters in 60 seconds each (typically 0-60). Interpretation: Higher scores indicate better performance.
Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A)
Time frame: Baseline and 12 weeks.
Description: Change in anxiety symptoms measured with the Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A; Zigmond \& Snaith, 1983). Scale range: 0-21 points. Interpretation: Higher scores indicate greater anxiety severity.
Beck Depression Inventory-II (BDI-II) - Total Score
Time frame: Baseline and 12 weeks.
Description: Change in depressive symptoms measured with the Beck Depression Inventory-II (BDI-II; Beck et al., 1996). Scale range: 0-63 points. Interpretation: Higher scores indicate greater depressive severity.
Inventario de Situaciones y Respuestas de Ansiedad (ISRA) - Total Score
Time frame: Baseline and 12 weeks.
Description: Change in cognitive, physiological, and motor anxiety responses measured with the Inventario de Situaciones y Respuestas de Ansiedad (ISRA; Miguel-Tobal \& Cano-Vindel, 1994). Scale range: 0-100+ (higher scores = greater anxiety response). Interpretation: Higher scores indicate greater anxiety reactivity.
8 secondary outcomes
Recent Life Changes Questionnaire (RLCQ) - Total Score
Time frame: Baseline and 12 weeks.
Symptom Checklist-90-Revised (SCL-90-R) - Global Severity Index (GSI)
Time frame: Baseline and 12 weeks.
Cognitive Triad Inventory (CTI) - Total Score
Time frame: Baseline and 12 weeks.
Intolerance of Uncertainty Scale (IUS) - Total Score
Time frame: Baseline and 12 weeks.
Social Support Questionnaire (SSQ-6) - Total Score
Time frame: Baseline and 12 weeks.
Pittsburgh Sleep Quality Index (PSQI) - Total Score
Time frame: Baseline and 12 weeks.
MRI Lesion Activity and Lesion Load
Time frame: Baseline and 12 weeks.
Duke-UNC Functional Social Support Questionnaire (DUFSS) - Total Score
Time frame: Baseline and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Background: PubMed 40833620Scandiffio J, Langer LK, Senthilnathan V, Feng G, Sureshkumar A, Bromberg M, Babineau J, Donkers SJ, Knox KB, Bruno T, Walker LAS, Bayley MT, Simpson R. Effects of psychological therapies in people with multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials. J Neurol. 2025 Aug 20;272(9):584. doi: 10.1007/s00415-025-13315-6.
- Background: PubMed 39276596Lucien A, Francis H, Wu W, Woldhuis T, Gandy M. The efficacy of cognitive behavioural therapy for depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2024 Nov;91:105858. doi: 10.1016/j.msard.2024.105858. Epub 2024 Sep 3.
- Background: PubMed 22516321Moss-Morris R, McCrone P, Yardley L, van Kessel K, Wills G, Dennison L. A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue. Behav Res Ther. 2012 Jun;50(6):415-21. doi: 10.1016/j.brat.2012.03.001. Epub 2012 Mar 13.
- Background: PubMed 39801437De Meo E, Portaccio E, Bonacchi R, Giovannoli J, Niccolai C, Amato MP. An update on the treatment and management of cognitive dysfunction in patients with multiple sclerosis. Expert Rev Neurother. 2025 Feb;25(2):227-243. doi: 10.1080/14737175.2025.2450788. Epub 2025 Jan 16.
- Background: PubMed 24679399Cuijpers P, Karyotaki E, Weitz E, Andersson G, Hollon SD, van Straten A. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis. J Affect Disord. 2014 Apr;159:118-26. doi: 10.1016/j.jad.2014.02.026. Epub 2014 Feb 24.
- Background: PubMed 23180174Amato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, Comi G. Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol. 2013 Jun;260(6):1452-68. doi: 10.1007/s00415-012-6678-0. Epub 2012 Nov 23.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) will be made available upon reasonable request to the corresponding author, Dr. Moisés Bermúdez Hernández (mbermudh@ull.edu.es), for academic and non-commercial research purposes. Data will be fully anonymized in compliance with institutional and ethical regulations and the European General Data Protection Regulation (GDPR).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) in people with Multiple Sclerosis (MS) - Relapsing-remitting and Anxiety, run by Moisés Bermúdez Hernández at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue Severity Scale (FSS) - Total Score (time frame: Baseline and 12 weeks.). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07273604, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026; AzTrials last refreshed its copy on 1 Nov 2026.