## Protocol Section
### Identification Module
**NCT ID:** NCT04090879

**Brief Title:** Low Nicotine Content Cigarettes in Vulnerable Populations: Affective Disorders

**Official Title:** Low Nicotine Content Cigarettes in Vulnerable Populations: Affective Disorders

#### Organization Study ID Info
**ID:** CHRMS19-0129
#### Organization
**Class:** OTHER
**Full Name:** Brown University
#### Secondary ID Infos
**ID:** U54DA036114-06
**Link:** https://reporter.nih.gov/quickSearch/U54DA036114-06
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2024-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-08-18

**Type:** ACTUAL

**Last Update Submit Date:** 2023-08-16

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2024-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2019-09-18

**Type:** ACTUAL

**Status Verified Date:** 2023-08

#### Study First Post Date
**Date:** 2019-09-16
**Type:** ACTUAL
**Study First Submit Date:** 2019-09-13
**Study First Submit QC Date:** 2019-09-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** FED

**Name:** Food and Drug Administration (FDA)

**Class:** NIH

**Name:** National Institute on Drug Abuse (NIDA)

**Class:** OTHER

**Name:** University of Vermont

#### Lead Sponsor

**Class:** OTHER

**Name:** Brown University

#### Responsible Party

**Investigator Affiliation:** Brown University

**Investigator Full Name:** Jennifer Tidey

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** While the prevalence of smoking in the United States general population has declined over the past 50 years, there has been little to no decline among people with mental health conditions. Affective Disorders (ADs) are the most common mental health conditions in the US, and over 40% of people with ADs are current smokers. A national policy of reducing the nicotine content of cigarettes has the potential to reduce tobacco use, dependence, and related adverse health outcomes. Controlled trials in psychiatrically-stable smokers have shown that reducing the nicotine content in cigarettes can reduce cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences.

The goal of the proposed trial is to experimentally model whether increasing the availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) moderates the effect of altering the nicotine in cigarettes in smokers with ADs. Additionally, investigators will test whether allowing participants to personalize the flavor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking.

Daily smokers with current ADs will be recruited at Brown University and the University of Vermont.

Investigators will study two research cigarettes referred to here as Research Cigarette 1 (RC1) and Research Cigarette 2 (RC2). One of these cigarettes will be a normal nicotine content cigarette and the other will be a reduced nicotine content cigarette. Investigators will study two e-cigarette conditions referred to here as E-Cigarette Condition 1 (EC1) and E-Cigarette Condition 2 (EC2). Both e-cigarette conditions will involve the same commercially available devices and same nicotine-containing e-liquid, but in one condition that e-liquid will be available only in tobacco flavor while in the other condition that e-liquid will be available in multiple flavors from which participants can choose based on personal taste preference. Participants will be assigned to one of the following four study conditions: (1) RC1 only; (2) RC2 only; (3) RC2 + EC1; (4) RC2 + EC2.

Participants will be asked to use only their assigned study products for 16 weeks. Outcome measures include total CPD, cigarette demand assessed by behavioral economics-based purchase tasks, craving, withdrawal, psychiatric symptoms, breath carbon monoxide (CO), biomarkers of tobacco toxicant exposure, brain function and structure, and airway inflammation (fractional nitric oxide concentration in exhaled breath \[FeNO\]).

### Conditions Module

**Conditions:**

- Tobacco Use Disorder

**Keywords:**

- Biomarkers of Exposure

- Compensatory Smoking

- Nicotine Dependence

- Reduced Nicotine Cigarettes

- Affective Disorders

- Tobacco Withdrawal

- Vulnerable Populations

- E-Cigarettes

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Randomized parallel groups research design

##### Masking Info

**Masking:** TRIPLE

**Masking Description:** Double blind dosing of tobacco cigarette nicotine levels.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 232

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Research Cigarettes #1

**Intervention Names:**

- Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

**Label:** RC 1 only

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Research Cigarettes #2

**Intervention Names:**

- Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

**Label:** RC 2 only

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Research Cigarettes #2 plus E-cigarettes #1 (participants receive tobacco flavor only)

**Intervention Names:**

- Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

- Other: E-Cigarettes

**Label:** RC 2 + EC 1

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Research Cigarettes #2 plus E-cigarettes #2 (participants can choose among varying flavors)

**Intervention Names:**

- Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

- Other: E-Cigarettes

**Label:** RC 2 + EC 2

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- RC 1 only

- RC 2 + EC 1

- RC 2 + EC 2

- RC 2 only

**Description:** 1) Altering the nicotine content of the tobacco research cigarette

**Name:** Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- RC 2 + EC 1

- RC 2 + EC 2

**Description:** 1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition

**Name:** E-Cigarettes

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Measure:** Cigarettes Per Day

**Time Frame:** 16 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria

* Between 21 years and 70 years old
* Must have current diagnosis of an Affective Disorder.

Exclusion Criteria

* Being without an Affective Disorder
* Younger than 21 years old
* Older than 70 years old

**Healthy Volunteers:** True

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Providence

**Country:** United States

**Facility:** Brown University

**State:** Rhode Island

**Zip:** 02912

**Location 2:**

**City:** Burlington

**Country:** United States

**Facility:** University of Vermont

**State:** Vermont

**Zip:** 05401

#### Overall Officials

**Official 1:**

**Affiliation:** Brown University

**Name:** Jennifer W Tidey, Ph.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019966

- Term: Substance-Related Disorders

- ID: D000064419

- Term: Chemically-Induced Disorders

- ID: D000001523

- Term: Mental 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: M21835

- Name: Mood Disorders

- Relevance: HIGH

- As Found: Affective Disorder

- ID: M16785

- Name: Tobacco Use Disorder

- Relevance: HIGH

- As Found: Tobacco Use Disorder

- ID: M21837

- Name: Substance-Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M30302

- Name: Chemically-Induced 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

### Condition Browse Module - Meshes

- ID: D000014029

- Term: Tobacco Use Disorder

- ID: D000019964

- Term: Mood Disorders

### Intervention Browse Module - Ancestors

- ID: D000005731

- Term: Ganglionic Stimulants

- ID: D000001337

- Term: Autonomic Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018722

- Term: Nicotinic Agonists

- ID: D000018679

- Term: Cholinergic Agonists

- ID: D000018678

- Term: Cholinergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CNSSti

- Name: Central Nervous System Stimulants

### Intervention Browse Module - Browse Leaves

- ID: M12478

- Name: Nicotine

- Relevance: HIGH

- As Found: Prior to

- ID: M4029

- Name: Central Nervous System Stimulants

- Relevance: LOW

- As Found: Unknown

- ID: M20796

- Name: Nicotinic Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M20758

- Name: Cholinergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000009538

- Term: Nicotine

### Misc Info Module

- Version Holder: 2024-05-24
