## Protocol Section
### Identification Module
**NCT ID:** NCT06424184

**Brief Title:** Accelerated rTMS for Substance Use Disorder and Depression

**Official Title:** Substance Use Disorder Treatment With Accelerated Repetitive Transcranial Magnetic Stimulation for Depression (START-D)

#### Organization Study ID Info
**ID:** STU-2024-0232
#### Organization
**Class:** OTHER
**Full Name:** University of Texas Southwestern Medical Center
### Status Module
#### Completion Date
**Date:** 2027-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Texas Southwestern Medical Center

#### Responsible Party

**Investigator Affiliation:** University of Texas Southwestern Medical Center

**Investigator Full Name:** Manish Jha

**Investigator Title:** Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** False

### Description Module

**Brief Summary:** This study is a small open-label feasibility trial of an accelerated course of repetitive transcranial magnetic stimulation (rTMS) for individuals with depression and stimulant use disorder \[including methamphetamine or cocaine use disorder (MUD/CUD)\].

**Detailed Description:** This research is an open label feasibility trial of accelerated course of repetitive transcranial magnetic stimulation (rTMS) for individuals with stimulant use disorder. Participants will be recruited from an existing and ongoing longitudinal study of stimulant use disorder (STIM-RAD) (NCT06073340). Prior to initiating the accelerated course of rTMS, participants will undergo screening procedures to evaluate eligibility. Those eligible will complete up to four (4) rTMS sessions of intermittent theta burst over left dorsolateral prefrontal cortex per day, up to five (5) days per week of the study, for a total of 50 sessions over a three (3) week period and will undergo electroencephalography (EEG), electrocardiography (ECG), urine drug screens, as well as self-report and clinician-rated assessments. A follow-up visit will be conducted 1 week after the last session of rTMS.

### Conditions Module

**Conditions:**

- Stimulant Use

- Depression

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Open label trial

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Eligible participants who are enrolled will receive an accelerated course of repetitive Transcranial Magnetic Stimulation.

**Intervention Names:**

- Device: Accelerated Repetitive Transcranial Magnetic Stimulation

**Label:** rTMS Intervention

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- rTMS Intervention

**Description:** The rTMS protocol implemented in this study will include approximately 10-minute long sessions of intermittent theta burst stimulation (iTBS) with at least 50 minutes in between iTBS sessions.

Study participants will receive the rTMS intervention for up to 50 sessions across a three-week period. The total of 50 sessions will be administered as up to 4 sessions each day, up to 5 days per week over an up to 3-week-long period.

**Name:** Accelerated Repetitive Transcranial Magnetic Stimulation

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Feasibility will be measured by completion of at least 30 out of 50 sessions of rTMS.

**Measure:** Feasibility of an accelerated course of repetitive Transcranial Magnetic Stimulation (rTMS).

**Time Frame:** 3 weeks

#### Secondary Outcomes

**Description:** Attainment of response is defined as 3 out of 5 negative urine samples for stimulants (cocaine, amphetamines), in week 3 of treatment.

**Measure:** Attainment of response of rTMS intervention on stimulant use assessed by Urine Drug Screens.

**Time Frame:** 1 week

**Description:** The Stimulant Craving Questionnaire (STCQ) is a 10-item self-report measure derived from the 10-item Cocaine Craving Questionnaire-Brief and the original 46-item Cocaine Craving Questionnaire-Now. The STCQ assesses current craving for stimulants (cocaine, methamphetamine, and other stimulants) using a seven-point scale, with answers ranging from "strongly disagree" to "agree."

**Measure:** Changes in stimulant craving during the 3-week treatment phase assessed by the Stimulant Craving Questionnaire (STCQ).

**Time Frame:** 3 weeks

**Description:** Craving for stimulants and other substances will be self-reported by participants on a Visual Analog Drug Craving Scale (VAS) which ranges from 0 (no craving) to 100 (most intense craving possible).

**Measure:** Changes in stimulant craving during the 3-week treatment phase assessed by a Visual Analog Drug Craving Scale (VAS).

**Time Frame:** 3 weeks

**Description:** Current craving for stimulants will be assessed using the Cue Craving Assessment. Participants will be asked about their current craving for and ability to resist stimulants on a 0-10 scale immediately after cue exposure prior to rTMS and after the completion of each rTMS session. A "0" rating indicates the absence of craving or the absence of the ability to resist use, whereas a "10" rating indicates the highest craving or strongest ability to resist use.

**Measure:** Changes in stimulant craving during the 3-week treatment phase assessed by the Cue Craving Assessment.

**Time Frame:** 3 weeks

**Description:** The Timeline Followback (TLFB) procedure will be used to elicit the participant's self-reported use of illicit substances, including but not limited to stimulants, and polysubstance use starting at the Screening Visit and continuing throughout study participation. During the Screening Visit, this form will be used to assess illicit use of substances for the 30-day period prior to written consent. During the study, TLFB will be administered to document the participant's self-reported use of illicit substances, nicotine, and tobacco for each visit since the previous TLFB assessment. Participant's drug of choice will be asked and determined by study coordinator and recorded along with the TLFB assessment.

**Measure:** Changes in frequency of self-reported stimulant use based on Timeline Followback (TLFB).

**Time Frame:** 6 weeks

**Description:** The Concise Health Risk Tracking - Self-Report (CHRT-SR) is a 14-item self-report assessment of suicidality and related thoughts and behaviors. The scale is designed to track suicidality quickly and easily in a manner consistent with the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Participants are asked to rate the extent that they have related to fourteen different statements on a scale of "strongly disagree" to "strongly agree." A higher score indicates higher suicidality.

**Measure:** Changes in self-reported symptoms of suicidality during the 3-week treatment phase.

**Time Frame:** 3 weeks

**Description:** The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) will assess overall depressive symptoms. The total score of QIDS-SR (range of 0-27) is based on the nine DSM-lV criteria symptom domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance, appetite/weight increase/decrease, and psychomotor agitation/retardation. Each question is scored on a 0-3 scale based on the participant's response. A higher score indicates higher depressive symptoms.

**Measure:** Changes in self-reported symptoms of depression during the 3-week treatment phase.

**Time Frame:** 3 weeks

**Description:** A 10-item version of the Concise Associated Symptom Tracking Scale Self-Report (CAST-IRR) will be used to assess associated mood symptoms. Participants are asked to rate the extent that they have related to ten different statements in the past week on a 5-point Likert scale (from 1, "strongly disagree," to 5, "strongly agree," where a higher score indicates increased symptoms). Some items in the CAST-IRR include: "I wish people would just leave me alone"; "I feel very uptight"; "I find myself saying or doing things without thinking"; "Lately everything seems to be annoying me"; and "I find people get on my nerves easily."

**Measure:** Changes in self-reported symptoms of irritability during the 3-week treatment phase.

**Time Frame:** 3 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Be aged 18-65 years, inclusive.
2. Be able to sufficiently understand, speak, and read English to provide informed consent and ask relevant questions, and be willing to comply with all study procedure instructions.
3. Self-report stimulant use (cocaine, methamphetamine, or prescription stimulants) at least 10 days in the 30-day period prior to consent.
4. Have a diagnosis of moderate or severe Cocaine or Methamphetamine Use Disorder (CUD/MUD) or other Stimulant Use Disorder over the past 12 months (as determined by the MINI International Neuropsychiatric Interview).
5. Have a PHQ9 of greater than or equal to five (5).
6. Be willing to provide urine samples, EEGs, and ECGs.
7. Be willing to use appropriate birth control method during the treatment phase of the study, if individual is of childbearing potential.

Exclusion Criteria:

1. Have a current pattern of alcohol, benzodiazepine, or other sedative/hypnotic use that would preclude safe participation in the study, as determined by the PI or their designee.
2. Have a history of a serious medical disorder that, in the opinion of the PI or their designee, would make it unsafe to participate in the study or may prevent collection of study data (e.g., disabling terminal diagnosis for which hospice care is being sought; serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy and/or is clinically stable on therapy, in the opinion of the PI or their designee, prior to study entry).
3. Have a documented history of unprovoked seizure (lifetime) or any seizure in the past 6 months.
4. Have a documented history of brain lesion(s) and/or tumor(s).
5. Have metal implants or non-removable metal objects above the neck.
6. Current pregnancy as determined by a urine screening.
7. Current or lifetime manic or hypomanic episode, defined by MINI diagnostic interview.
8. Current psychotic disorder.
9. Are a prisoner or in police custody at the time of eligibility screening.

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Taylor.Helmbrecht@UTSouthwestern.edu

**Name:** Taylor Helmbrecht, B.S.A.

**Phone:** (214) 998-6504

**Role:** CONTACT

**Contact 2:**

**Email:** Teresa.Slettebo@UTSouthwestern.edu

**Name:** Teresa Slettebo, B.A.

**Phone:** (214) 998-5649

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Dallas

**Country:** United States

**Facility:** UT Southwestern Medical Center

**State:** Texas

**Zip:** 75247

#### Overall Officials

**Official 1:**

**Affiliation:** UT Southwestern Medical Center

**Name:** Manish Jha, M.B.B.S

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Northrup TF, Green C, Walker R, Greer TL, Trivedi MH. On the invariance of the Stimulant Craving Questionnaire (STCQ) across cocaine and methamphetamine users. Addict Behav. 2015 Mar;42:144-7. doi: 10.1016/j.addbeh.2014.11.020. Epub 2014 Nov 25.

**PMID:** 25462663

**Citation:** Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health. 1990 Aug;13(4):227-36. doi: 10.1002/nur.4770130405.

**PMID:** 2197679

**Citation:** Sobell LC, Sobell MB, Leo GI, Cancilla A. Reliability of a timeline method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations. Br J Addict. 1988 Apr;83(4):393-402. doi: 10.1111/j.1360-0443.1988.tb00485.x. No abstract available.

**PMID:** 3395719

**Citation:** Trivedi MH, Wisniewski SR, Morris DW, Fava M, Gollan JK, Warden D, Nierenberg AA, Gaynes BN, Husain MM, Luther JF, Zisook S, Rush AJ. Concise Health Risk Tracking scale: a brief self-report and clinician rating of suicidal risk. J Clin Psychiatry. 2011 Jun;72(6):757-64. doi: 10.4088/JCP.11m06837.

**PMID:** 21733476

**Citation:** Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007 Jul;164(7):1035-43. doi: 10.1176/ajp.2007.164.7.1035.

**PMID:** 17606655

**Citation:** Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003 Sep 1;54(5):573-83. doi: 10.1016/s0006-3223(02)01866-8. Erratum In: Biol Psychiatry. 2003 Sep 1;54(5):585.

**PMID:** 12946886

**Citation:** Rush AJ, Bernstein IH, Trivedi MH, Carmody TJ, Wisniewski S, Mundt JC, Shores-Wilson K, Biggs MM, Woo A, Nierenberg AA, Fava M. An evaluation of the quick inventory of depressive symptomatology and the hamilton rating scale for depression: a sequenced treatment alternatives to relieve depression trial report. Biol Psychiatry. 2006 Mar 15;59(6):493-501. doi: 10.1016/j.biopsych.2005.08.022. Epub 2005 Sep 30.

**PMID:** 16199008

**Citation:** Trivedi MH, Wisniewski SR, Morris DW, Fava M, Kurian BT, Gollan JK, Nierenberg AA, Warden D, Gaynes BN, Luther JF, Rush AJ. Concise Associated Symptoms Tracking scale: a brief self-report and clinician rating of symptoms associated with suicidality. J Clin Psychiatry. 2011 Jun;72(6):765-74. doi: 10.4088/JCP.11m06840.

**PMID:** 21733477

**Citation:** Jha MK, Minhajuddin A, South C, Rush AJ, Trivedi MH. Irritability and Its Clinical Utility in Major Depressive Disorder: Prediction of Individual-Level Acute-Phase Outcomes Using Early Changes in Irritability and Depression Severity. Am J Psychiatry. 2019 May 1;176(5):358-366. doi: 10.1176/appi.ajp.2018.18030355. Epub 2019 Mar 29.

**PMID:** 30922100

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001526

- Term: Behavioral Symptoms

- ID: D000019964

- Term: Mood Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000064419

- Term: Chemically-Induced Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC25

- Name: Substance Related Disorders

### Condition Browse Module - Browse Leaves

- ID: M7058

- Name: Depression

- Relevance: HIGH

- As Found: Depression

- ID: M7061

- Name: Depressive Disorder

- Relevance: HIGH

- As Found: Depression

- ID: M21837

- Name: Substance-Related Disorders

- Relevance: HIGH

- As Found: Substance Use Disorders

- ID: M4818

- Name: Behavioral Symptoms

- Relevance: LOW

- As Found: Unknown

- ID: M21835

- Name: Mood Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M30302

- Name: Chemically-Induced Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000019966

- Term: Substance-Related Disorders

- ID: D000003863

- Term: Depression

- ID: D000003866

- Term: Depressive Disorder

### Misc Info Module

- Version Holder: 2024-05-31
