Efficacy of Reboxetine and Methylphenidate Treatment on Attentional, Sensory and Emotional Dysregulation in Adults With PTSD

NCT05133804 | Recruiting Phase 2

• 1 other identifier: LH9/2019
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

Brief Summary

Up-to-date, no studies have examined the attentional, sensory and emotional processing (difficulties) among patients diagnosed with Posttraumatic Stress Disorder (PTSD). In addition, the efficiency of drug treatments that focus on the noradrenergic and dopaminergic, and thus influence attention processing and PTSD symptoms through these pathways, have only briefly been investigated. There is well-established and long-standing evidence for the involvement of dopamine and noradrenaline in attentional function. This previously led to an investigation by the investigator's research lab in which the investigators hypothesized the involvement of an attentional disorder would influence PTSD symptoms in a rat model. Based on these results, the current study aims to characterize attentional deficits in patients with PTSD, as well as the correlation between attention, emotional regulation and sensory processing. The investigators do this partially by conducting a case-control study and through a subsequent double-blind RCT (with only the cases). The patients will be either treated with reboxetine + methylphenidate or placebo.

Conditions

Posttraumatic Stress Disorder

Keywords

Posttraumatic Stress Disorder; Attention Deficit; Sensory Processing; Emotion Regulation; Methylphenidate; Reboxetine; Randomized Controlled Trial; Electroencephalogram; Functional near-infrared spectroscopy

Outcome Measures

Primary Outcomes (1)

• Change in Clinician-Administered Posttraumatic Stress Disorder Scale for the Diagnostic and Statistical Manual (DSM)-5 (CAPS-5) between baseline score (before treatment) and score on day 26 (after treatment)

  PTSD symptom severity score. Total of 56 questions. Minimum score 0, maximum score 80. A higher score reflects a worse outcome.

  Day 1 and day 26

Secondary Outcomes (10)

• Posttraumatic Stress Disorder Symptom Scale (PSS-SR5)

  Day 1 and day 26

• Conner's Adult ADHD Rating Scales - Self Report: short version (CAARS-S:S)

  Day 1 and day 26

• Electroencephalography (EEG)

  Day 1, day 21 and day 26

• Functional near-infrared spectroscopy (fNIRS)

  Day 1, day 21 and day 26

• Electrodermal Activity (EDA)

  Day 1, day 21 and day 26

Study Arms (2)

Treatment with Reboxetine and Methylphenidate

EXPERIMENTAL

During the first 3 weeks of the study, subjects in the active treatment group will take reboxetine at a dose of 4mgper day, with the instructions to start at 2mg per day for 3 days and then increase the dosage to 4mg per day for 26 days, i.e. until completion of the study. On day 22 of the study, the patients will take the first dosage of10mg Ritalin or a placebo, and remain in the clinic for 2 hours to guard safety and guidance during possible occurrence of side effects such as anxiety, palpitations, etc. During the observation time in the clinic, 6 Ritalin IR 10mg and 3 Reboxetine 4mg pills will be handed out to the participants. These pills will be taken at the responsibility of the subject at8:00 AM (Ritalin and Reboxetine) and at noon (Ritalin only) at the following three days.

Drug: Methylphenidate; Drug: Reboxetine

Treatment with Placebo

PLACEBO COMPARATOR

The patients will take placebos according to the medication schedule of the treatment group.

Drug: Placebo

Interventions

Methylphenidate DRUG

Ritalin 10mg

Also known as: Ritalin

Treatment with Reboxetine and Methylphenidate

Reboxetine DRUG

Reboxetine 4mg

Treatment with Reboxetine and Methylphenidate

Placebo DRUG

Placebo matched to Reboxetine

Also known as: Placebo matched to Reboxetine

Treatment with Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• diagnosed with PTSD according to DSM-IV or DSM-5 criteria
• current treatment at the outpatient facilities of Lev HaSharon Netanya Adult Clin
• age between 20 and 60 years
• no present-day re-exposure to the traumatic event
• any psychotropic drug therapy that is being administered must be at a fixed dose for at least one month prior to the study conductance

You may not qualify if:

• comorbid major psychiatric disorder, e.g. psychotic disorder, unipolar or bipolar disorder, borderline personality disorder, or active suicidal ideation,
• ADHD diagnosis,
• significant or severe systematic disease that limits normal activity, e.g. autoimmune disease, AIDS or renal failure,
• cardiovascular disease, e.g. hypertension, atrioventricular (AV) block, bradycardia, or conduction disorder,
• severe disease that is a threat to life, e.g. acute myocardial infarction, respiratory failure, or cancer,
• nervous system impairment, e.g. multiple sclerosis, Alzheimer's disease, Parkinson's disease, epilepsy, or stroke,
• previous or current severe traumatic brain injury,
• glaucoma,
• impaired hearing,
• active substance dependency including regular use of medical cannabis,
• use of steroid medication in the two months prior to study conductance,
• use of medication that may affect the function of the central nervous system,
• failure to complete all research steps

Sponsors & Collaborators

• University of Haifa: lead

Study Sites (3)

Emek Medical Center

Afula, Israel

RECRUITING

University of Haifa

Haifa, Israel

RECRUITING

Lev HaSharon Mental Health Center

Netanya, Israel

RECRUITING

Related Publications (2)

• Aga-Mizrachi S, Cymerblit-Sabba A, Gurman O, Balan A, Shwam G, Deshe R, Miller L, Gorodetsky N, Heinrich N, Tzezana O, Zubedat S, Grinstein D, Avital A. Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model. Transl Psychiatry. 2014 Sep 23;4(9):e447. doi: 10.1038/tp.2014.82.

  PMID: 25247592 BACKGROUND

• McAllister TW, Zafonte R, Jain S, Flashman LA, George MS, Grant GA, He F, Lohr JB, Andaluz N, Summerall L, Paulus MP, Raman R, Stein MB. Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. Neuropsychopharmacology. 2016 Apr;41(5):1191-8. doi: 10.1038/npp.2015.282. Epub 2015 Sep 11.

  PMID: 26361060 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Attention Deficit Disorder with Hyperactivity; Emotional Regulation

Interventions

Methylphenidate; Reboxetine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Self-Control; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines

Study Officials

• Avi Avital, PhD

  University of Haifa

  PRINCIPAL INVESTIGATOR

• Batya Engel-Yeger, PhD

  University of Haifa

  PRINCIPAL INVESTIGATOR

• Inbal Brenner, MD

  Lev HaSharon Mental Health Center

  PRINCIPAL INVESTIGATOR

• Tsipi Milman, MD

  Emek Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Avi Avital, PhD

CONTACT

+972-4-8420-364; avitalavi@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor at Department of Occupational Therapy; Head of Behavioral Neurobiology lab

Model Details: Patients will be randomized into two groups: either treatment with medication or treatment with placebo. In addition, within each group patients will be randomized into a group for EEG recording and a group for fNIRS recording. This is a non-interventional randomization.

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: November 24, 2021
• Study Start: June 1, 2022
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3)