Transcranial Magnetic Stimulation for Methamphetamine Use Disorder During Pregnancy

Developing Transcranial Magnetic Stimulation as a Therapeutic Modality for Methamphetamine Use Disorder During Pregnancy

The goal of this clinical trial is to learn whether transcranial magnetic stimulation, also called TMS, is a practical and acceptable treatment option for methamphetamine use disorder during pregnancy. The study will enroll pregnant women who have methamphetamine use disorder.

The main questions it aims to answer are:

1. Can pregnant women with methamphetamine use disorder be successfully enrolled and complete TMS treatment?
2. Is TMS acceptable to pregnant participants, their caregivers or partners, and clinicians involved in their care?
3. Is it feasible to collect maternal and infant health information during pregnancy and after delivery?

Researchers will compare standard 4-week TMS, accelerated 2-week TMS, and treatment as usual to see which approach is more practical and better tolerated during pregnancy.

Participants will:

• Be randomly assigned to receive standard TMS, accelerated TMS, or treatment as usual.
• Complete study visits during pregnancy and follow-up visits after treatment.
• Complete questionnaires about substance use, cravings, mood, anxiety, sleep, quality of life, and side effects.
• Provide urine drug tests and have vital signs and safety assessments completed.
• Allow the study team to review pregnancy and infant medical records.
• Some participants will complete interviews about their experiences and views of TMS during pregnancy.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy; Methamphetamine Use Disorder
• Intervention / Treatment: Device: 4- Week Dual-Target Transcranial Magnetic Stimulation (TMS); Device: Accelerated Dual-Target Transcranial Magnetic Stimulation (aTMS); Other: Treatment as Usual (TAU)

Detailed Description

This is a three-arm, randomized, controlled feasibility trial evaluating transcranial magnetic stimulation (TMS) as a potential treatment for methamphetamine use disorder (MaUD) during pregnancy. The study aims to 1) assess the feasibility of recruitment, retention, and intervention delivery among pregnant women with MaUD, 2) assess the feasibility of collecting maternal health outcomes, and 3) assess the feasibility of collecting postnatal neonatal outcomes.

Up to 45 pregnant participants will be enrolled and randomized in equal proportions (1:1:1) to: (1) standard TMS (16 sessions over 4 weeks), (2) accelerated TMS (aTMS; 16 sessions over 2 weeks), or (3) treatment as usual (TAU). The TAU group will continue with existing care, including contingency management, behavioral counseling, and other standard treatments available in the community. Randomization will be stratified based on the presence of co-occurring substance use disorders and implemented using a secure REDCap randomization module with permuted block allocation. Participants will be followed through pregnancy and until 6 months postpartum.

Eligible participants are pregnant women aged 22 years and older with a diagnosis of active methamphetamine use disorder and a gestational age of 34 weeks or less at enrollment. Participants with contraindications to TMS or medical or psychiatric conditions that substantially increase risk, including seizure disorders, bipolar I disorder, schizophrenia spectrum disorders, or active alcohol use disorder, will be excluded.

All TMS procedures will be conducted at the Huntsman Mental Health Institute using a TMS system with theta burst stimulation capabilities. Treatment will utilize a dual-target stimulation approach consisting of excitatory intermittent theta burst stimulation (iTBS) directed at the dorsolateral prefrontal cortex (DLPFC) and inhibitory continuous theta burst stimulation (cTBS) directed at the medial prefrontal cortex (mPFC). Stimulation intensity will be individualized using each participant's resting motor threshold and gradually increased during initial treatment sessions as tolerated.

Participants randomized to the standard TMS arm will receive 16 treatment sessions delivered over 4 weeks. Participants randomized to the accelerated TMS arm will receive the same total number of treatment sessions delivered over 2 weeks using an accelerated treatment schedule. Participants assigned to treatment as usual will continue receiving available evidence-based clinical care without TMS.

The primary feasibility outcomes include recruitment rates, screening completion, enrollment rates, randomization success, retention throughout treatment and follow-up, completion of TMS sessions, participant adherence, and completion of study assessments. Acceptability outcomes include participant satisfaction, treatment burden, and willingness to participate in future TMS studies.

Maternal outcomes will be collected throughout pregnancy and during follow-up and will include measures of methamphetamine use frequency, substance use severity, craving, depression, anxiety, sleep quality, quality of life, cognitive functioning, urine drug testing results, and physical health indicators. Data will be collected using validated self-report instruments, clinical assessments, medical record review, and biologic measures where applicable.

Neonatal outcomes will be assessed through medical record review and follow-up assessments and will include gestational age at delivery, birth weight, Apgar scores, neonatal intensive care unit admission, neonatal length of stay, and developmental outcomes through 6 months postpartum. Infant development will be evaluated using the Ages and Stages Questionnaire, Third Edition (ASQ-3), and supplemented by pediatric health record review when available.

This study is not powered to evaluate treatment efficacy. Rather, the purpose of the study is to establish the feasibility and acceptability of TMS for methamphetamine use disorder during pregnancy and to determine the feasibility of collecting maternal and neonatal outcome data needed for a future fully powered randomized clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rana Jawish, MD; Phone Number: 8015878626; Email: rana.jawish@hsc.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women age 22 years and older who are pregnant with a singleton pregnancy
• >12 weeks and ≤ 34 weeks gestational age at screening
• Diagnosis of MaUD in the past 12 months
• Participant must have engaged in perinatal care (through family medicine, Obstetrics/Gynecology, Internal Medicine, etc) during this pregnancy
• Capacity to consent
• Capacity to complete all study procedures

Exclusion Criteria:

• Unable to receive the TMS treatment (e.g. have metal implants, metal device(s) in their head or body, cochlear implants, implanted brain stimulators, aneurysm clips). Dental implants that are TMS safe are not exclusionary)
• Lifetime diagnosis of schizophrenia, bipolar disorder, schizoaffective disorder, or psychosis
• Actively suicidal or homicidal
• Active heavy alcohol use
• Using any medication that significantly increases the risk of seizure by lowering seizure threshold (for example Wellbutrin over 300 mg daily) or antipsychotics
• History of epilepsy, a personal history of seizures, or a family history of epilepsy or seizure in a first degree relative
• History of intracranial hemorrhage, stroke in the past 12 months, intracranial mass, or head trauma in the past 12 months
• History of or current diagnosis of chronic hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg), and/or history of or current diagnosis of preeclampsia
• Moderate to severe heart disease
• Any medical condition that in the PI's opinion will interfere with the study or increase risk to the participant
• Current participation in another clinical trial (excluding large population-based or observational studies like All of Us)
• Not able to complete the protocol due to travel, work, etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Dual-Target TMS; Participants receive 16 sessions of dual-target transcranial magnetic stimulation (TMS) delivered over 4 weeks. Treatment includes intermittent theta burst stimulation (iTBS) to the dorsolateral prefrontal cortex (DLPFC) followed by continuous theta burst stimulation (cTBS) to the medial prefrontal cortex (mPFC).	Device: 4- Week Dual-Target Transcranial Magnetic Stimulation (TMS); Participants will receive dual-target TMS delivered sequentially to the DLPFC and mPFC. Target localization will follow the international 10-20 EEG system using the Beam F3 and FP1 positions, consistent with prior studies. Each session will include iTBS to the DLPFC administered as 2-second trains of 50-Hz triplets delivered at 5 Hz, with an 8-second intertrain interval, totaling 600 pulses, and cTBS to the mPFC consisting of continuous 50-Hz triplets totaling 600 pulses. A total of 16 sessions will be delivered: one/day treatments for 5 days during weeks 1-2, followed by one/day treatments for 3 days during weeks 3-4.
Experimental: 2-week Dual-Target TMS; Participants will receive dual-target TMS delivered sequentially to the DLPFC and mPFC. Target localization will follow the international 10-20 EEG system using the Beam F3 and FP1 positions, consistent with prior studies. Each session will include iTBS to the DLPFC administered as 2-second trains of 50-Hz triplets delivered at 5 Hz, with an 8-second intertrain interval, totaling 600 pulses, and cTBS to the mPFC consisting of continuous 50-Hz triplets totaling 600 pulses. A total of 16 sessions will be delivered: 3-4 sessions/day (with 30-60 minutes between sessions) delivered on 4-5 treatment days within a 2-week timeframe.	Device: Accelerated Dual-Target Transcranial Magnetic Stimulation (aTMS); Dual-target theta burst TMS delivered using a Elevate TMS cTMS001 system. Each treatment session includes excitatory intermittent theta burst stimulation (iTBS) to the dorsolateral prefrontal cortex and inhibitory continuous theta burst stimulation (cTBS) to the medial prefrontal cortex. Participants receive 16 treatment sessions over 2 weeks using an accelerated treatment schedule.
Active Comparator: Treatment as Usual; Participants continue receiving standard clinical care for methamphetamine use disorder during pregnancy without study-administered TMS.	Other: Treatment as Usual (TAU); Treatment as usual consists of existing evidence-based treatment approaches available in the community, including contingency management, behavioral counseling, and medications when clinically indicated. Participants do not receive study-administered TMS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Recruitment	Feasibility of recruitment will be assessed by measuring enrollment rates (participants enrolled divided by eligible participants)	Pre-enrollment through 6-month follow-up
Feasibility of Retention	Feasibility of retention will be assessed by measuring retention rates (completion of greater than or equal to 80% of 16 TMS sessions) in the TMS groups.	Pre-enrollment through 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of collecting maternal outcomes	Feasibility of collecting maternal outcomes will be defined as collecting greater than or equal to 80% of outcomes.	Baseline through 6-month follow-up
Feasibility of collecting neonatal outcomes	Feasibility of collecting neonatal outcomes will be defined as collecting greater than or equal to 80% of outcomes.	Birth through maternal 6-month follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Outcomes - Methamphetamine Use timeline Follow-Back	Exploration of trends in maternal methamphetamine use over time and between groups including change in methamphetamine use (timeline Follow-Back)	Baseline through 6-month follow-up
Neonatal outcomes - birth weight	Exploration of trends in neonatal outcomes between groups including weight at birth (lbs).	Birth
Safety Measures - adverse events	Incidence, severity, and relatedness of adverse events and serious adverse events from baseline or experienced since the last visit	baseline through 6-month follow-up
Maternal Outcomes - Methamphetamine Use (urine drug test)	Exploration of trends in maternal methamphetamine use over time and between groups including change in methamphetamine use (results of urine drug test)	Screen through 6-month follow-up
Maternal Outcomes - cravings (Stimulant Craving Questionnaire - SCQ)	Exploration of trends in maternal methamphetamine cravings over time and between groups including change in score on SCQ	Screen through 6-month follow-up
Maternal Outcomes - mental health (Patient Health Questionnaire-9 - PHQ-9)	Exploration of trends in maternal outcomes across time and between groups including change in mental health (change in PHQ-9 score)	Baseline through 6-month follow-up
Maternal Outcomes - mental health (Generalized Anxiety Disorder-7 - GAD-7)	Exploration of trends in maternal outcomes across time and between groups including change in mental health (change in GAD-7 score)	Baseline through 6-month follow-up
Maternal Outcomes - sleep health (Pittsburgh Sleep Quality Index - PSQI)	Exploration of trends in maternal outcomes across time and between groups including change in sleep health (change in PSQI score)	Screen through 6-month follow-up
Maternal Outcomes - quality of life and satisfaction (Quality of Life Enjoyment and Satisfaction Questionnaire - Q-LES-Q-SF)	Exploration of trends in maternal outcomes across time and between groups including change in quality of life and satisfaction (change in Q-LES-Q-SF score)	Baseline through 6-month follow-up
Maternal Outcomes - physical health indicators (blood pressure)	Exploration of trends in maternal outcomes across time and between groups including change in physical health indicators (change in blood pressure)	Baseline through 6-month follow-up
Maternal Outcomes - physical health indicators (weight gain)	Exploration of trends in maternal outcomes across time and between groups including change in physical health indicators (change in weight in lbs)	Baseline through 6-month follow-up
Maternal Outcomes - physical health indicators (gestational diabetes)	Exploration of trends in maternal outcomes across time and between groups including diagnosis of gestational diabetes	Screen through 6-month follow-up
Neonatal outcomes - gestational age at birth	Exploration of trends in neonatal outcomes between groups including gestational age at birth (weeks)	Birth
Neonatal outcomes - Apgar scores	Exploration of trends in neonatal outcomes between groups including Apgar scores at birth	Birth
Neonatal outcomes - NICU admission and length of stay	Exploration of trends in neonatal outcomes between groups including incidence of NICU admission and length of stay at birth	Birth
Neonatal outcomes - neurodevelopment (Ages and Stages Questionnaire, Third Edition (ASQ-3))	Exploration of trends in neonatal outcomes across time and between groups including neurodevelopment as assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3) at 2, 4 and 6 months after birth.	Birth through 6-month follow-up
Safety measures - Columbia Suicide Severity Rating Scale (C-SSRS)	Suicidal ideation and behavior will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS)	Screen through post birth 6-month follow-up

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rana Jawish, MD, Utah, University of

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: August 25, 2026
• First Submitted That Met QC Criteria: September 24, 2026
• First Posted (Actual): September 30, 2026

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 24, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Substance Use Disorder; Transcranial Magnetic Stimulation (TMS); Pregnant Women; Maternal Health; Neonatal Outcomes; Stimulant Use Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Therapeutics
• Other Study ID Numbers: IRB_00202011; K23DA065955-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data underlying published results will be shared, including demographic information, maternal and neonatal health outcomes, substance use measures, mental health assessments, TMS treatment adherence data, and qualitative interview data that have been de-identified in accordance with IRB approval and participant consent. Supporting documentation including data dictionaries, codebooks, study protocols, and analytic code will also be made available.

IPD Sharing Time Frame

Data will be available no later than publication of the primary study outcomes or at the conclusion of the funding period, whichever occurs first, and will remain available indefinitely.

IPD Sharing Access Criteria

De-identified participant-level data will be available through The Hive repository at the University of Utah. Data sharing will comply with University of Utah and NIH policies. Data identified as sensitive or potentially re-identifiable may require controlled access, including data use agreements and IRB approvals when applicable.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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