Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Related to Breast Cancer (ONCODEP)

Cognitive Impairment Clinical Trial

— ONCODEP  

Official title:

Intervention With Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Associated With Breast Cancer (ONCODEP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06053775
• Other study ID #: 2023/213
• Secondary ID: FPU21/00082
• Status: Recruiting
• Phase: N/A
• Start date: September 27, 2023
• Est. completion date: September 2025

Study information

• Verified date: November 2023
• Source: University of Santiago de Compostela
• Contact: María Teresa Carrillo de la Peña
• Phone: +34 647344231
• Email: mteresa.carrillo[@]usc.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test a home-delivered intervention that combines Non-Invasive Brain Stimulation techniques (transcranial direct and alternating current stimulation -tDCS and tACS-) and Online Cognitive Training (OCT) to treat depressive symptomatology and cognitive decline associated with breast cancer. The main questions aims to be answered are:

• To analyze the efficacy and feasibility of the intervention to treat depressive symptomatology.

• To analyze the efficacy and feasibility of the intervention to treat cognitive decline.

• To evaluate the medium and long-term effects (1, 3 and 6 months) of intervention.

An OCT program and a portable wireless tDCS/tACS system will be used to perform the intervention at home. Patients will be divided into four treatment groups, depending on whether they will receive the OCT applied independently or combined with tDCS/tACS active or sham.

In addition, saliva samples will be collected to identify bomarkers predictive of treatment efficacy.

Description:

This study is aimed at analyzing the feasibility and therapeutic efficacy of a home-based treatment using tDCS/tACS and an OCT program to treat depressive symptomatology (primary outcome variable) associated with breast cancer.The effect of the intervention on the patients' cognitive functioning (secondary outcome variable) will be also studied. In addition, saliva biomarkers and other clinical variables will be analyzed to determine whether they are related to the response to treatment. Finally, the impact of the intervention on the burden of the relatives/caregivers will be studied.

Oncology Units of the Galician Health Service will be contacted for recruitment. Oncologists will review whether patients meet the inclusion criteria and none of the exclusion criteria. If so, patients will be given an information flyer and will contact the research team to receive more information and, if they wish, to participate in the study. If patients are interested in participating, researchers will contact them to confirm the inclusion/exclusion criteria and participants will be invited to the first face-to-face session. In this session, informed consent will be signed, pre-treatment neuropsychological assessment will be performed, medical data will be reviewed, and a saliva sample will be collected. After collecting this data, the first treatment session will take place in the presence of the researcher. The type of treatment each patient will receive (OCT, tDCS active+ OCT, tACS active+ OCT or sham neurostimulation+ OCT. ) will be chosen randomly, using a randomization list.

After that, each patient will undergo 14 sessions, daily, at home. The tES devices (Soterix Medical Inc) have been designed for home use and allow the application of the stimulation by the patient himself, while being monitored by the researcher. The OCT will be delivered through NeuronUp2GO platform.Possible adverse effects associated with neurostimulation (which are mild and transitory) and other variables that may affect its efficacy (medication diary, caffeine intake...) will be monitored daily.

Finally, a post-treatment assessment will be carried out 15 days after the start of treatment and a follow-up assessment will be carried out 1, 3 and 6 months after the end of treatment. The 15-day and 1 month assessments will be the same as the pre-treatment (questionnaries and neuropsychological test). The follow-ups at 3 and 6 months will be done online, by filling in questionnaires.

Both the treatment administration and analysis of the results will be blinded.

First, descriptive analyses will be performed on the sociodemographic and clinical data. To evaluate the efficacy of the treatments on depressive symptomatology and subjective cognitive complaints, ANOVAs will be calculated under classical and Bayesian statistical frameworks, with Group (4 arms) as inter-participant factor and Time (pre, post, 1, 3 and 6 months follow-up) as intra-participant factor, following an Intention-to-Treat approach (including possible missing data after randomization). ANOVAs will also be calculalted with with Group (4 arms) as inter-participant factor and Time (pre, post, 1 month follow-up) as intra-participant factor to calculate the efficacy of the treatments on neuropsychological indexes. The possible modulating effect of sociodemograpchic and clinical variables on treatment efficacy will be analyzed. Also, for the clinical validation of the treatments, the analysis of the Minimal Clinically Important Difference (MCID) at short (15 days), medium (1 month) and long term (3 and 6 months) will be included. The difference between the pre- and post-treatment assessment in the primary and secondary variable scores should be equal to or greater than 30%.

Proteomic analysis will be performed at the Fundación Biomédica Galicia Sur. The following analysis will be performed: determination of total protein, mass spectrometry and electrophoretic separation of the samples by SDS-PAGE and identification of the bands of interest by Shotgun. The whole sample will be analyzed in liquid mass spectrometer (LC-MS/MS). Linear or logistic regression analysis will be performed to determine the predictive power of the saliva biomarkerson treatment efficacy.

Since the present research involves adult humans, it will be conducted under applicable international, EU and national laws and regulations (The Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects; The International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) Guidelines; the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine; and the UNESCO Universal Declaration on Bioethics and Human Rights (2005). Permission has been obtained from the local IRB committee (CEIm de Galicia) to conduct the study.

In terms of data protection, this study complies with the directives of the General Data Protection Regulation (GDPR), approved by the European Commission on April 27, 2016 (EU 2016/679) and with the Organic Law 3/2018, of December 5, 2018, on the Protection of Personal Data and guarantees of digital rights. The storage and treatment of the samples will be carried out in accordance with the Biomedical Research Law 14/2007 and RD 1716/201.

Patients' clinical data will be collected in the study-specific data collection notebook using REDCap (Research Electronic Data Capture), a secure web-based application for building and managing online surveys and databases. Data collection will be pseudo-anonymous, protecting the identity of the participant. Only the principal investigator of the entity responsible for data collection (USC) will know the pseudonymization codes. The research team will have access to all coded data collected for the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of breast cancer in early stages (life expectancy greater than 12 months).

• Patients who are receiving or have finished (maximum 6 months prior to participation in the participating in the study) some type of oncological treatment (Chemotherapy, Radiotherapy, Immunotherapy, Hormonal Therapy).

• Patients whose mother tongue is Galician or Spanish.

• Ability to give informed consent.

• Present depressive symptomatology: score of 4 or higher in the BDI-FS.

• Ability to use WhastApp

• Have access to some technology (desktop computer, laptop or tablet) and the Internet (Firefox or Chrome browsers).

Exclusion Criteria:

• Pregnant or breastfeeding women.

• Patients with metastasis.

• Patients with a history of psychiatric symptomatology (depressive disorder, bipolar,anxious, psychotic...) prior to the oncological process.

• Patients with a history of cognitive impairment or dementia prior to the oncologic process.

oncological process.

• Patients with a history of neurosurgery, cortical lesions or neurological alterations prior to the oncological process.

• Patients with history or current consumption of non-prescribed drugs.

• Patients with the following medication regimen: mood stabilizers, antipsychotics, anticonvulsants, l-dopa, rivastigmine, dextromethorphan, flunarizine, sulpiride, use of benzodiazepines (excluding long half-life benzodiazepines (Bromazepam, Diazepam) on a continuous/habitual basis,Alprazolam >1mg per day, Lorazepam >2mg per day).

• Patients taking antidepressant medication should have a stable regimen ( same medication at the same dose for a minimum of four weeks prior to entering the study.The regimen with antidepressant drugs or drugs used as treatment to improve cognition should be kept stable during the entire participation (until the follow-up evaluation has been performed).

• Patients unable to complete a neuropsychological examination.

• Patients who are participating in a research study/clinical trial with drugs.

• Patients who present any condition contraindicated to undergo tES (intracranial ferromagnetic devices or implanted stimulators; history of active epilepsy; history of neurosurgery, traumatic brain injury with loss of brainwith loss of consciousness and/or cortical lesion) (Antal et al., 2017)

Related Conditions & MeSH terms

• Cognitive Impairment
• Depression
• Depressive Symptoms

Intervention

Device:
• Transcranial Direct Current Stimulation
tDCS+OCT
• Transcranial Alternating Current Stimulation
tACS+OCT
• tES sham
tES sham + OCT
• Online Cognitive Training
OCT

Locations

Country	Name	City	State
Spain	University of Santiago de Compostela	Santiago De Compostela	A Coruña
Spain	Fundación Biomédica Galicia Sur	Vigo	Pontevedra

Sponsors (2)

Lead Sponsor	Collaborator
University of Santiago de Compostela	Fundacin Biomedica Galicia Sur

Country where clinical trial is conducted

Spain, 

References & Publications (5)

Cheng ASK, Wang X, Niu N, Liang M, Zeng Y. Neuropsychological Interventions for Cancer-Related Cognitive Impairment: A Network Meta-Analysis of Randomized Controlled Trials. Neuropsychol Rev. 2022 Dec;32(4):893-905. doi: 10.1007/s11065-021-09532-1. Epub 2022 Jan 29. — View Citation

Gaynor AM, Pergolizzi D, Alici Y, Ryan E, McNeal K, Ahles TA, Root JC. Impact of transcranial direct current stimulation on sustained attention in breast cancer survivors: Evidence for feasibility, tolerability, and initial efficacy. Brain Stimul. 2020 Jul-Aug;13(4):1108-1116. doi: 10.1016/j.brs.2020.04.013. Epub 2020 Apr 27. — View Citation

Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29. — View Citation

Moffa AH, Martin D, Alonzo A, Bennabi D, Blumberger DM, Bensenor IM, Daskalakis Z, Fregni F, Haffen E, Lisanby SH, Padberg F, Palm U, Razza LB, Sampaio-Jr B, Loo C, Brunoni AR. Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109836. doi: 10.1016/j.pnpbp.2019.109836. Epub 2019 Dec 16. — View Citation

Rodella C, Bernini S, Panzarasa S, Sinforiani E, Picascia M, Quaglini S, Cavallini E, Vecchi T, Tassorelli C, Bottiroli S. A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment. Aging Clin Exp Res. 2022 Jan;34(1):73-83. doi: 10.1007/s40520-021-01912-0. Epub 2021 Jun 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Digit Span Test (forward and backward) (Barcelona Test-Revised)	To assess the verbal span and working memory with series of digits in increasing and decreasing order (5 minutes).	pre-, post- intervention (15 days) and follow up (1 month)
Other	Spain-Complutense Verbal Learning Test (TAVEC)	To examine recent and delayed verbal learning and memory delayed (30 minutes,including the delay between trials).	pre-, follow-up (1 month)
Other	Verbal fluency test (NEURONORMA Project)	To assess lexical and semantic fluency and executive components of language (5 minutes).	pre-, post- intervention (15 days) and follow up (1 month)
Other	Salthouse Perceptual Comparison Test (SPCT)	To examine perceptual comparison and processing speed (3 minutes).	pre-, post- intervention (15 days) and follow up (1 month)
Other	Dual task	Evaluate the response cost of performing a task individually or while performing it simultaneously. The tasks consist of recalling a series of digits in direct order and letter and symbol cancellation tasks.(5 minutes).	pre-, post- intervention (15 days) and follow up (1 month)
Other	d2-R (Test of Attention-Revised)	To assess examines selective attention and concentration using a cancellation task (10 minutes)	pre-, post- intervention (15 days) and follow up (1 month)
Other	Generalized Anxiety Disorder-7 scale (GAD-7)	To assess anxious symptomatology (7 items, scored on a Likert scale from 0 to 3). Scores range between 0 and 21, with higher scores indicating higher anxious symptomatology.	pre-, post- intervention (15 days) and follow-up (1 month)
Other	PROMIS Fatigue 7a	To examine presence of fatigue symptoms (7 items, scored on a Likert scale from 1 to 5). Scores range between 7 and 35, with lower scores indicating higher fatigue symptoms.	pre-, post- intervention ( 15 days) and follow-up (1 month)
Other	EORTC QLQ-C30	The QLQ-C30 is composed of both multi-item scales and single-item measures. The questionnaire icludes five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients.; All of the scales and single-item measures range in score from 0 to 100.; A high scale score represents a higher response level: A high score for a functional scale represents a high / healthy level of functioning,; A high score for the global health status / QoL represents a high QoL,; A high score for a symptom scale / item represents a high level of symptomatology / problems.	pre-, post- intervention (15 days) and follow-up (1,3,6 months)
Other	Pittsburgh Sleep Quality Index (PSQI)	To assess sleep quality and disturbances over a 1-month. The questionnaire includes 19 items, combined to form seven scales to evaluate different components of sleep (subjective quality, latency, duration, efficiency, disturbances, medication use, sleep dysfunction). Each scale obtain a score that ranges from 0 to 3 (0- no difficulty, 3- severe difficulty). The 7 components are summed to obtain an overall quality o sleep score, from 0 to 21 points (0 - no difficulty, 21 - severe difficulty).	pre-, post- intervention (15 days) and follow-up (1 month)
Other	Zarit (Caregiver Burden Interview)	To assess the burden (stress and negative feelings) associated with the caregiving task. It is composed of 22 items answered according to a Likert scale range from 0 to 4. The cut-off point for caregiver burden is 46-47.; It also makes a distinction between mild burden (up to 56) and heavy burden (more than 56).	pre-, post- intervention (15 days) and follow-up (1,3,6 months)
Other	Pain: ad-hoc questionnaire	It measures the change in pain intensity, interference and discomfort afeter the treatment. There are three scales (intensity, interference, discomfort), which score range from 1 (no pain, no interference, no discomfort) to 10 (unbearable pain, interferes greatly and very unpleasant). Lower scores indicate a lower presence of pain symptoms.	pre-, post- intervention (15 days) and follow-up (1 month)
Other	Self-efficacy: ad-hoc questionnaire	To analyze general and cognitive self-efficacy. 7 items scored on a Likert scale from 1 to 5. A higher score reflects greater confidence in achieving certain self-efficacy related goals.	pre-, post- intervention (15 days) and follow-up ( 1 month)
Other	Global improvement assessment: ad-hoc questionnaire	To know the subjective perception of improvement after treatment in terms of cognitive functioning, mood, fatigue, quality of sleep and quality of life. Each question is answered on a scale from 1 (no improvement) to 10 (great improvement).	post- intervention (15 days) and follow-up (1, 3, 6 months)
Primary	Beck Depression Inventory- Fast Screen (BDI-FS)	Screening of depressive symptoms in medical patients (7 items, scored on a Likert scale from 0 to 3). BDI-FS minimum and maximum values range from 0 to 21, with higher scores meaning more depressive symptomatology.	pre-, post- intervention (15 days) and follow-up (1,3,6 months)
Secondary	Patient Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8a	To assess subjective cognitive complaints in the last week (8 items, scored on a Likert scale from 1 to 5). Minimum and maximum values rang from 8 to 40. Lower scores mean more subjective cognitive complaints.	pre-, post- intervention (15 days) and follow-up (1,3,6 months)
Secondary	Montreal Cognitive Assessment (MoCA)	Cognitive impairment screening that explores attention, concentration, executive functions, memory, language, visual-constructive abilities, calculation and orientation (10 minutes). Minimum and maximum values range from 0 to 30. Lower scores mean better cognitive functioning, The cutoff point for Mild Cognitive Impairment is 26.	pre-, post- intervention (15 days) and follow-up (1month).

External Links

•   tACS for the treatment of MDD