Effect of HF rTMS on Serum BDNF in Cocaine Use Disorder

Cocaine Dependence Clinical Trial

Official title:

Effects of 5-Hz Repetitive Transcranial Magnetic Stimulation on Serum Brain Derived Neurotrophic Factor and Clinical Variables in Cocaine Use Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06189690
• Other study ID #: TMS-Coc-BDNF
• Status: Recruiting
• Phase: N/A
• Start date: January 6, 2022
• Est. completion date: December 1, 2027

Study information

• Verified date: December 2023
• Source: Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
• Contact: Erik D. Morelos-Santana, Ph D. Candidate
• Phone: 5255416053503
• Email: emorelos[@]imp.edu.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to explore the effect of 5-Hz rTMS over the left dorsolateral prefrontal cortex on the BDNF, craving and cognitive function. This study will be longitudinal, with a short-term double-blind placebo-controlled phase consisting of 20 rTMS sessions and a long-term phase, consisting of 2 weekly sessions for 12 weeks. Participants will be clinically assessed pre-treatment (T0), after 20-sessions phase (T1) and after 12-weeks phase (T2) by an interview about psychiatric symptoms. Also, blood will be obtained in the same T0, T1 and T2 to peripheral levels of BDNF determination. Cognitive state will be measured at the same time-points (T0, T1, T2) by paper-pencil and computerized neuropsychological assessment. Researchers will compare active rTMS versus placebo 5 Hz-rTMS on described variables. Additionally, a comparative group (without rTMS intervention) will be included to equivalently measure described variables during periods without cocaine consumption.

Description:

Brain derived neurotrophic factor (BDNF) is a widely explored neurotrophin in preclinical models of cocaine addiction with relevant phase and region dependent dynamics along addictive cycle. In humans with cocaine use disorder (CUD), peripheral BDNF have revealed relationship with relevant treatment outcomes as relapse and time of abstinence. In CUD several interventional studies using high frequency repetititve transcranial magnetic stimulation (rTMS) have shown craving reduction, mood improvements and sustained modifications in functional conectivity measued by fMRI. Due to the relevance of BDNF in CUD, and neuroplasticity-related processes derived from rTMS interventions, this study aims to determine changes in peripheral BDNF, craving, cognition in CUD in reponse to rTMS. Aditionally, other outcomes will be considered as depression, anxiety and motivational changes.

Procedure: Psychiatric clinical and cognitive assessment, and blood collection will be performed at T0, T1 and T2 time-points. Short-term rTMS phase will consist of two weeks (weekdays) with 2 rTMS or rTMS-placebo sessions (detaills in arms section). Then, two sessions per week along 12 weeks as maintenance therapy will be considered. No rTMS group will attend the same time points and assessment in a controlled facility.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 1, 2027
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Current cocaine use disorder according to the Diagnostic and statistical manual of mental disorders (DSM 5).

2. Cocaine crack or powder use for at least 12 months with a frequency of 3 times or more per week, with abstinence periods shorter than 1 year for the last year.

3. Primary school completed.

Exclusion Criteria:

1. Personal or first degree family history of any neurological disorder including, but not limited to, organic brain syndrome, epilepsy, brain injuries, multiple sclerosis, conditions that increase intracranial pressure.

2. Personal history of brain surgery or traumatic brain injury.

3. Comorbilities that could represent a risk of neuroinfection or increased convulsive threshoid.

4. Other than alcohol, tobacco or marijuana substance use disorder.

5. If the patient does not meet the safety criteria for rTMS.

6. Current use of any medication that might provoque seizures or any anticonvulsant drugs.

7. Personal history of schizophrenia, mania/hypomania or OCD.

8. Personal history of myocardial infarction, angina, congestive heart failure, cerebrovascular events, transient ischemic attack or any other heart condition currently undergoing medical treatment.

9. Personal history of seizures or detection of paroxysmal EEG activity.

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders

Intervention

Device:
• rTMS
Repetitive TMS will be administered by a MagPro R30 stimulator and an active/placebo MCF-B70 A/P coil. All participants will use two surface electrodes to simulate rTMS skin sensations near to stimulation site. rTMS/sham conditions will be double-blinded by a USB stick. The USB contains the information about rTMS/sham condition and this is not available to the stimulator operator. Parameters of rTMS were previously described.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Psiquiatría Ramón de la Fuente M.	Ciudad de mexico	Tlalpan

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente	National Council of Science and Technology, Mexico

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Psychological problems	The self-administered 90-item Symptoms Checklist-90 (SCL90) will be used.	T0 before the intervention, T1: after rTMS2 weeks, T2: after 12 weeks maintenance phase
Other	Addiction severity	The structured interview Addiction Severity Index Lite (ASI-Lite) wil be used to evaluate severity regarding the use of drugs and alcohol.	T0 before the intervention, T1: after rTMS2 weeks, T2: after 12 weeks maintenance phase
Other	Previous cocaine-crack comsumption	A retrospective calendar-based self report will be used to measure days of consumption previous to the study enrollment.	T0 before the intervention, T1: after rTMS2 weeks, T2: after 12 weeks maintenance phase
Other	Motivation to change	The 32-item self-administered form of University of Rhode Island Change Assessment (URICA) will be used.	T0 before the intervention, T1: after rTMS2 weeks, T2: after 12 weeks maintenance phase
Primary	BDNF	Serum BDNF levels will be measured by an ELISA kit following the manufacturer's instructions.	T0 before the intervention, T1: after rTMS 2 weeks, T2: after 12 weeks maintenance phase
Primary	Cocaine craving	The Cocaine Craving Questionnaire (CCQ) in the general and now versions will be used to measure craving. Additionally, the visual analog scale (VAS) to cocaine/crack desire consumption will be used as craving measurement.	T0 before the intervention, T1: after rTMS 2 weeks, T2: after 12 weeks maintenance phase
Secondary	Depression	The 17-item Hamilton Depression Rating Scale (HAM-D) will be used,	T0 before the intervention, T1: after rTMS 2 weeks, T2: after 12 weeks maintenance phase
Secondary	Anxiety	The 14-item Hamilton Anxiety Rating Scale (HAM-A) will be used.	T0 before the intervention, T1: after rTMS2 weeks, T2: after 12 weeks maintenance phase