Cognitive Remediation Therapy in Schizophrenia: Effects on Epigenetics

Epigenetic Regulation of Brain-Derived Neurotrophic Factor (BDNF) Gene Expression According to Response to Cognitive Remediation in Schizophrenia

This study is a randomised and controlled trial that aims to investigate whether Cognitive Remediation Therapy (CRT) can modulate epigenetic mechanisms by changing methylation levels of BDNF gene in patients with Schizophrenia.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Behavioral: Cognitive Remediation Therapy

Detailed Description

OBJECTIVES: To investigate whether Cognitive Remediation Therapy (CRT) can modulate epigenetic mechanisms by changing methylation levels of BDNF gene. It also aims to test whether BDNF valine-66-methionine (Val66Met) polymorphism influences CRT treatment outcome among people with schizophrenia.

SAMPLE AND METHODS: A randomized and controlled study will be carried out with two groups: patients receiving CRT and patients in control condition without any cognitive intervention and receiving Treatment as Usual (TAU). Methylation levels of BDNF gene at different sites will be contrasted before and after treatment. Additionally, neurocognition profile, level of symptoms and psychosocial functioning will also be tested. CRT outcomes will be investigated in a mixed model for repeated measures.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia according to DSM-5 and confirmed by the semi-structured interview (SCID) for the axis 1.
• Presence of cognitive impairment confirmed by the neuropsychological battery
• Stable symptomatology at least during the last six months and the estimation of not modifying pharmacological antipsychotic treatment .

Exclusion Criteria:

• Presence of organic-cerebral affectation due to neurological or traumatic conditions
• Antipsychotic dose change >10%
• Abuse of psychotropic substances
• Presence of other psychiatric symptomatology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Remediation Therapy; Cognitive Remediation Therapy. CRT will be based on CIRCuiTS, a computerized program.	Behavioral: Cognitive Remediation Therapy; "CIRCuiTS is a web-based computerised CR therapy, delivered by a therapist but supplemented with independent sessions to facilitate massed practice. It targets metacognition, particularly strategy use, in addition to providing massed practice of basic cognitive functions. The therapist facilitates motivation, metacognitive and strategy development and generalisation of learning by encouraging the participant to learn about and regulate their cognitive performance and to transfer this learning to meet real-world goals. Therapists provide additional scaffolding for CR tasks to ensure consistent successful performance. Independent sessions involve carrying out cognitive tasks allocated by the therapist to ensure scaffolded learning" (Reeder et al.2017); Other Names: CIRCuiTS
No Intervention: Treatment as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in methylation at Cytosine-phosphate-Guanine (CpG) exon	Mean methylation percentage in CpG island BDNF CpG exon I: located at chr11:27743473-27744564 in the BDNF	Baseline and after 4 months
Change in methylation at CpG exon IV	Mean methylation percentage of CpG region BDNF CpG exon IV: located at chr11:27723060-27723294 in exon IV, upstream of the start codon in exon VII	Baseline and after 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognition	Total score in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery	Baseline and after 4 months
Change in Symptoms	Total score in Positive and Negative Syndromes Scale (PANSS)	Baseline and after 4 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: National Alliance for Research on Schizophrenia and Depression; Instituto de Salud Carlos III
• Investigators: Principal Investigator: Rafael Penadés, PhD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2017
• Primary Completion (Anticipated): May 5, 2020
• Study Completion (Anticipated): June 15, 2020

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cognitive Remediation; BDNF; Epigenetics
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 24618; PI17/00872 (Other Grant/Funding Number: Instituto de Salud Carlos III)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No