Effect of rTMS on Neurotrophines Levels in CUD

NCT05824221 | Unknown

• 1 other identifier: brainbdnf
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Brief Summary: Background: Cocaine use disorders (CUD) is a multifactoral disease, involving several brain areas. One of the most investigated is the Dorsolateral Prefrontal Cortex (DLPFC) involved in impulsiveness control. Effective treatments for CUD are still needed and repetitive Transcranial Magnetic Stimulation (rTMS) is widely studied for its potential in reducing cocaine craving and consumption. Objectives: The main outcome is to test if rTMS can be related to neuroplasticity and neurotrophism through changes in Brain-Derived Neurotrophic Factor (BDNF) and its precursor (pro-BDNF) levels. Eligibility: Healthy, right-handed adults ages 18-65 who do have cocaine use disorder (moderate to severe). Design: This is a randomized, sham-controlled study. The study includes a rTMS continued treatment phase compared to healthy control (HC) evaluation. Prior to participating, participants will be screened with:

• Medical history
• Anamnestic sheet
• Physical exam
• Urine tests After being enrolled, participants and HC will undergo venous blood sample (BDNF and proBDNF levels). During the continued rTMS phase, participants with cocaine use disorder will be randomized to receive real or sham rTMS; a former arm is also provided and is made up of HC. RTMS will be delivered in 10 days, over 2 weeks (5 days/week). After the last rTMS session a blood sample for neurotrophines levels will be collected. Treatment includes:
• rTMS: A coil is placed on the head. At each session, participants will receive two rTMS sessions, with a 50 mins interval. At the beginning of each rTMS session, they view cocaine-related images for few minutes (cue-induced stimuli).
• BDNF/proBDNF levels: A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period (first two weeks), this sample will be also collected from HC. The blood sample will be centrifuged within 20 minutes of sampling at 1000 × g for 15 minutes. Then, the serum will be aliquoted and stored at -80 ° C until analysis.
• Urine toxicological screen

Conditions

Cocaine Use; Cocaine Dependence; Cocaine Abuse; Neurotropism

Keywords

rTMS; BDNF; proBDNF; Cocaine Use Disorder

Outcome Measures

Primary Outcomes (3)

• Change in BDNF level (biological marker)

  BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. The increase in serum levels of BDNF seems to reflect the neuroplasticity of the CUD brain. BDNF measurements will be calculated in pg/ml

  Baseline, two weeks

• Change in proBDNF level (biological marker)

  Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml.

  Baseline, two weeks

• Change in pro-BDNF/BDNF ratio (biological marker)

  Pro-BDNF/BDNF ratio, seems to be a more specific measurement of the early changes in the metabolism of BDNF. Its level seems to correlate to more or less a neurotrophic and neuroprotective action of BDNF. As a ratio it has not a unit measure.

  Baseline, two weeks

Study Arms (3)

Active rTMS (15 Hz)

EXPERIMENTAL

Active stimulation of LDLPFC (15 Hz; 100% of RMT; 40 trains with 60 stimuli per train; inter-train interval of 15 second, total duration 13 minutes). Each session will be repeated twice/daily for 10 consecutive days for 2 weeks, during the continued treatment phase. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Device: rTMS

Sham rTMS

SHAM COMPARATOR

A pre-programmed software set sham stimulation by a staff member that will not be involved in data collection and analysis. The sham condition will match the number of pulses delivered during the 15Hz session and will use the same coil placement but the intensity of stimulation will be set a 3% of the RMT so to ensure that the participant will feel similar scalp sensations experienced by participants receiving active rTMS, but brain tissue will not be stimulated. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Device: rTMS

Healthy Control

NO INTERVENTION

Subject without diagnosis of Cocaine Use Disorder or other major psychiatric disorder.

Interventions

rTMS DEVICE

Non invasive brain stimulation in Cocaine Use Disorder

Active rTMS (15 Hz); Sham rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current diagnosis of cocaine use disorder (from moderate to severe), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);
• Abstinence from cocaine for at least 48 hrs.

You may not qualify if:

• Current DSM-5 diagnosis of substance and/or alcohol use disorders other than nicotine;
• Current DSM-5 diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;
• Use in the past 4 weeks of any medication with known pro-convulsant action; or current regular use of any psychotropic medications (benzodiazepines, antipsychotic medications, tricyclic antidepressants, anti-epileptics, mood stabilizers);
• Any history of any clinically significant neurological disorder, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery, or personal history of head trauma that resulted in loss of consciousness for \> 5 minutes and retrograde amnesia for \> 30 minutes;
• \. 18-65 years
• Current DSM-5 diagnosis of substance use disorders other than nicotine;
• Current DSM-5 diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;

Sponsors & Collaborators

• ITAB - Institute for Advanced Biomedical Technologies: lead

Study Sites (1)

ITAB

Chieti, 66100, Italy

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Mauro Pettorruso, MD, PhD

CONTACT

+393391979487; mauro.pettorruso@unich.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: With regard to the treatment, to ensure that both participants and investigators are blind to the condition (active or sham), the selection of the operation mode (15 Hz, sham) will be pre-programmed by member of the that will not be involved in data collection and analysis. Study personnel will not know which mode is being activated. Sham stimulation will use the same coil placement as that used for active stimulation. Outcomes Assessors will not be present during the rTMS sessions.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized, sham-controlled with a 1:1 allocation into 2 parallel arms. A third arm constituted by healthy patients.

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: April 21, 2023
• Study Start: April 30, 2023
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)