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THC Crossover Study (TRDRP)

Primary Purpose

THC, Cannabis, Cannabis Smoking

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Smoked Cannabis
Vaped Cannabis
Tobacco Cigarette
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for THC focused on measuring vape, cannabis, tobacco cigarette, thc, marijuana, smoking

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy on the basis of medical history and limited physical examination, as described below:

Heart rate < 105 beats per minute (BPM); Systolic Blood Pressure < 160 and > 90*; Diastolic Blood Pressure < 100 and > 50*

*Considered out of range if both machine and manual readings are above/below these thresholds.

  • Current regular user of cannabis who smokes cannabis as joint or blunt at least 3 times a week for past 3 months
  • History of cannabis vaporizer use or willingness to use the vaporizer in the study
  • Current tobacco cigarette use who smokes ≥ 5 cigarettes per day
  • Saliva cotinine ≥ 50 ng/ml
  • Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use

Exclusion Criteria:

  • Unstable medical conditions:

Heart disease; Uncontrolled hypertension; Thyroid disease (okay if controlled with medication); Diabetes; Hepatitis B or C or Liver disease; Glaucoma; Prostatic hypertrophy

  • Psychiatric conditions:

Current or past schizophrenia, and/or current or past bipolar disorder; Adult onset attention deficit hyperactivity disorder (ADHD); Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion; History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval

  • Concurrent regular use of smokeless tobacco or pipes [occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study]
  • Medications:

Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).; Concurrent use of nicotine-containing medications; Psychiatric medications: current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate.

  • Other/Misc. Chronic Health Conditions:

Oral thrush; Fainting; Untreated thyroid disease; Other "life threatening illnesses" as per study physician's discretion

  • Pregnancy:

Pregnancy (self-reported and urine pregnancy test); Breastfeeding (determined by self-report)

  • Drug/Alcohol Dependence:

Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program; Positive toxicology test at the screening visit (THC & prescribed medications okay); Methadone replacement therapy

  • Concurrent participation in another clinical trial
  • Inability to communicate in English
  • History of marijuana-induced psychosis or paranoia after smoking marijuana
  • Scoring a 2 or higher on the Severity of Dependence Scale for cannabis use
  • Planning to quit smoking or vaping within the next 60 days

Sites / Locations

  • Zuckerberg San Francisco General HospitalRecruiting
  • University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette

Either of the 2 remaining products

Remaining product

Arm Description

Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr cardiovascular (CV) monitoring Circadian blood draws 12-hr urine collection

Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr CV monitoring Circadian blood draws 12-hr urine collection

Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr CV monitoring Circadian blood draws 12-hr urine collection

Outcomes

Primary Outcome Measures

Peak plasma concentration
To assess the differences between smoked and vaped cannabis, we will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Time to peak plasma concentration
To assess the differences of these variables between smoked and vaped cannabis, we will determine the time to max concentration (Tmax) using plasma THC concentrations from the standardized sessions.
Area under the plasma concentration versus time curve (AUC)
To assess the differences of these variables between smoked and vaped cannabis, we will determine the AUC using plasma THC concentrations from the standardized sessions.
Subjective effects between cannabis products using the Marijuana Cravings Questionnaire
We will assess measures from the Marijuana Cravings Questionnaire (MCQ) and compare them between smoked and vaped cannabis.
Subjective effects between cannabis products using the Visual Analog Scale
We will assess measures from the Visual Analog Scale (VAS) and compare them between smoked and vaped cannabis.
Subjective effects between cannabis products using the Drug Effects Questionnaire
We will assess measures from the Drug Effects Questionnaire (DEQ) and compare them between smoked and vaped cannabis.
Max change of expired carbon monoxide
We will examine differences in max change of expired carbon monoxide (CO) from day 1 between smoked and vaped cannabis.
Area under the expired carbon monoxide (CO) curve (AUC)
We will examine differences in integrated AUC of expired carbon monoxide from day 1 between smoked and vaped cannabis.
Differences in metabolites of volatile organic compounds (VOCs)
We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (from day 2) between smoked and vaped cannabis.
Exposure to toxicants between cannabis products
We will also examine how measures of use (number of puss, amount use, number of use episodes) correlate with biomarker concentrations between smoked and vaped cannabis.
Cardiovascular effects between cannabis products using heart rate as a measure
We will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 30 minutes after the standardized session (day 1) between smoked and vaped cannabis.
Cardiovascular effects between cannabis products using epinephrine as a measure
Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines and compared between smoked and vaped cannabis.
Cardiovascular effects between cannabis products using platelet activation as a measure
We will examine differences in blood and urine biomarkers of platelet activation between smoked and vaped cannabis.
Cardiovascular effects between cannabis products using oxidant stress as a measure
We will examine differences in blood and urine biomarkers of oxidant stress between smoked and vaped cannabis.
Cardiovascular effects between cannabis products using endothelial dysfunction as a measure
We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked and vaped cannabis.

Secondary Outcome Measures

Toxicant exposure between smoked tobacco and cannabis using expired carbon monoxide as the measure
We will examine differences in expired carbon monoxide (CO) from day 1 (both max change and integrated AUC of expired CO) between smoked tobacco and cannabis.
Toxicant exposure between smoked tobacco and cannabis using mercapturic acid as the measure
We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (VOCs) (from day 2) between smoked tobacco and cannabis.
Toxicant exposure between smoked tobacco and cannabis using use as a measure
We will also examine how measures of use (number of puffs, amount use, number of use episodes) correlate with biomarker concentrations between smoked tobacco and cannabis.
Cardiovascular effects between smoked tobacco and cannabis using heart rate as a measure
We will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 30 minutes after the standardized session (day 1) between smoked tobacco and cannabis.
Cardiovascular effects between smoked tobacco and cannabis using epinephrine as a measure
Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines.
Cardiovascular effects between smoked tobacco and cannabis using platelet activation as a measure
We will examine differences in blood and urine biomarkers of platelet activation between smoked tobacco and cannabis.
Cardiovascular effects between smoked tobacco and cannabis using oxidant stress as a measure
We will examine differences in blood and urine biomarkers of oxidant stress between smoked tobacco and cannabis.
Cardiovascular effects between smoked tobacco and cannabis using endothelial dysfunction as a measure
We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked tobacco and cannabis.
Puffing behaviors across all products
We will examine how puffing behaviors are different between all products (smoked and vaped cannabis, as well as with smoked tobacco cigarettes) and how they correlate with toxicant biomarker concentrations. Vaping topography measures will be obtained from frame by frame analysis of high definition videos.

Full Information

First Posted
August 20, 2019
Last Updated
August 15, 2023
Sponsor
University of California, San Francisco
Collaborators
Tobacco Related Disease Research Program
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1. Study Identification

Unique Protocol Identification Number
NCT04429568
Brief Title
THC Crossover Study
Acronym
TRDRP
Official Title
Cardiovascular Effects of Cannabis Compared to Tobacco Use
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 30, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Tobacco Related Disease Research Program

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized, crossover study enrolling experienced dual cannabis-tobacco smokers (N=18) to describe the differences in THC and toxicant exposure, examining pharmacokinetic, subjective, and cardiovascular effects from smoking and vaping dry herb cannabis. This study will also examine the differences in toxicant exposure and cardiovascular disease risk between smoking cannabis and smoking tobacco cigarettes.
Detailed Description
Experienced dual cannabis-tobacco smokers will participate in a within-subject crossover study with three blocks: smoked cannabis (purchased by participants from a local dispensary), dry herb cannabis vaporizer, and usual brand tobacco cigarette. Each block will consist of 2 consecutive days on an inpatient research ward. The first inpatient day of each block will comprise of two sessions: (1) The first session will be a standardized bout to compare pharmacokinetic, physiologic, and subjective effects of cannabis and tobacco use; (2) after 6 hours of abstinence, the second session will be ad libitum access to the assigned product for 2 hours to compare subjective effects (reward, satisfaction, craving reduction) and use patterns. The second inpatient day will consist of ad libitum use of the assigned product from 8:00 in the morning to midnight. An abstinence day will be added after the second day of the last block to assess exposure and effects biomarkers during a period of abstinence from cannabis (smoked/vaped) or tobacco.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
THC, Cannabis, Cannabis Smoking, Cannabis Use, Unspecified, Cigarette Smoking, Tobacco Use, Nicotine Dependence, Nicotine Withdrawal, Cardiovascular Risk Factor
Keywords
vape, cannabis, tobacco cigarette, thc, marijuana, smoking

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette
Arm Type
Other
Arm Description
Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr cardiovascular (CV) monitoring Circadian blood draws 12-hr urine collection
Arm Title
Either of the 2 remaining products
Arm Type
Other
Arm Description
Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr CV monitoring Circadian blood draws 12-hr urine collection
Arm Title
Remaining product
Arm Type
Other
Arm Description
Abstinence from any product night before hospital admission Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette 6-hr abstinence and blood draws (PK) 2 hr Free use session w/ video monitoring Free use of assigned product 12-hr CV monitoring Circadian blood draws 12-hr urine collection
Intervention Type
Other
Intervention Name(s)
Smoked Cannabis
Intervention Description
Cannabis will be purchased by the participants and reimbursed the full cost by the study. Participants will be asked to purchase enough to last 2 full days of use. To reduce variability between products, participants will be asked to purchase cannabis from one dispensary near the research facility (Purple Star MD at 2520 Mission St., San Francisco). Receipt must be provided to study staff.
Intervention Type
Other
Intervention Name(s)
Vaped Cannabis
Intervention Description
Cannabis will be purchased by the participants and reimbursed the full cost by the study. Participants will be asked to purchase enough to last 2 full days of use. To reduce variability between products, participants will be asked to purchase cannabis from one dispensary near the research facility (Purple Star MD at 2520 Mission St., San Francisco). Receipt must be provided to study staff. All participants will use the study-provided PAX® (PAX 2) dry herb vaporizer, one of the most popular handheld vaporizers.
Intervention Type
Other
Intervention Name(s)
Tobacco Cigarette
Intervention Description
Tobacco cigarettes of participants' choice (usual brand) will be provided by research staff for use on the study.
Primary Outcome Measure Information:
Title
Peak plasma concentration
Description
To assess the differences between smoked and vaped cannabis, we will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Time Frame
Day 1 of each arm
Title
Time to peak plasma concentration
Description
To assess the differences of these variables between smoked and vaped cannabis, we will determine the time to max concentration (Tmax) using plasma THC concentrations from the standardized sessions.
Time Frame
Day 1 of each arm
Title
Area under the plasma concentration versus time curve (AUC)
Description
To assess the differences of these variables between smoked and vaped cannabis, we will determine the AUC using plasma THC concentrations from the standardized sessions.
Time Frame
Day 1 of each arm
Title
Subjective effects between cannabis products using the Marijuana Cravings Questionnaire
Description
We will assess measures from the Marijuana Cravings Questionnaire (MCQ) and compare them between smoked and vaped cannabis.
Time Frame
Days 1-2 of each arm
Title
Subjective effects between cannabis products using the Visual Analog Scale
Description
We will assess measures from the Visual Analog Scale (VAS) and compare them between smoked and vaped cannabis.
Time Frame
Days 1-2 of each arm
Title
Subjective effects between cannabis products using the Drug Effects Questionnaire
Description
We will assess measures from the Drug Effects Questionnaire (DEQ) and compare them between smoked and vaped cannabis.
Time Frame
Days 1-2 of each arm
Title
Max change of expired carbon monoxide
Description
We will examine differences in max change of expired carbon monoxide (CO) from day 1 between smoked and vaped cannabis.
Time Frame
Days 1-2 of the cannabis arms
Title
Area under the expired carbon monoxide (CO) curve (AUC)
Description
We will examine differences in integrated AUC of expired carbon monoxide from day 1 between smoked and vaped cannabis.
Time Frame
Days 1-2 of the cannabis arms
Title
Differences in metabolites of volatile organic compounds (VOCs)
Description
We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (from day 2) between smoked and vaped cannabis.
Time Frame
Days 1-2 of the cannabis arms
Title
Exposure to toxicants between cannabis products
Description
We will also examine how measures of use (number of puss, amount use, number of use episodes) correlate with biomarker concentrations between smoked and vaped cannabis.
Time Frame
Days 1-2 of the cannabis arms
Title
Cardiovascular effects between cannabis products using heart rate as a measure
Description
We will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 30 minutes after the standardized session (day 1) between smoked and vaped cannabis.
Time Frame
Day 1 of each arm
Title
Cardiovascular effects between cannabis products using epinephrine as a measure
Description
Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines and compared between smoked and vaped cannabis.
Time Frame
Day 2 of each cannabis arm
Title
Cardiovascular effects between cannabis products using platelet activation as a measure
Description
We will examine differences in blood and urine biomarkers of platelet activation between smoked and vaped cannabis.
Time Frame
Day 2 of each cannabis arm
Title
Cardiovascular effects between cannabis products using oxidant stress as a measure
Description
We will examine differences in blood and urine biomarkers of oxidant stress between smoked and vaped cannabis.
Time Frame
Day 2 of each cannabis arm
Title
Cardiovascular effects between cannabis products using endothelial dysfunction as a measure
Description
We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked and vaped cannabis.
Time Frame
Day 2 of each cannabis arm
Secondary Outcome Measure Information:
Title
Toxicant exposure between smoked tobacco and cannabis using expired carbon monoxide as the measure
Description
We will examine differences in expired carbon monoxide (CO) from day 1 (both max change and integrated AUC of expired CO) between smoked tobacco and cannabis.
Time Frame
Day 1 of each arm
Title
Toxicant exposure between smoked tobacco and cannabis using mercapturic acid as the measure
Description
We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (VOCs) (from day 2) between smoked tobacco and cannabis.
Time Frame
Day 2 of each arm
Title
Toxicant exposure between smoked tobacco and cannabis using use as a measure
Description
We will also examine how measures of use (number of puffs, amount use, number of use episodes) correlate with biomarker concentrations between smoked tobacco and cannabis.
Time Frame
Days 1-2 of each arm
Title
Cardiovascular effects between smoked tobacco and cannabis using heart rate as a measure
Description
We will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 30 minutes after the standardized session (day 1) between smoked tobacco and cannabis.
Time Frame
Day 1 of each arm
Title
Cardiovascular effects between smoked tobacco and cannabis using epinephrine as a measure
Description
Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines.
Time Frame
Day 2 of each arm
Title
Cardiovascular effects between smoked tobacco and cannabis using platelet activation as a measure
Description
We will examine differences in blood and urine biomarkers of platelet activation between smoked tobacco and cannabis.
Time Frame
Day 2 of each arm
Title
Cardiovascular effects between smoked tobacco and cannabis using oxidant stress as a measure
Description
We will examine differences in blood and urine biomarkers of oxidant stress between smoked tobacco and cannabis.
Time Frame
Day 2 of each arm
Title
Cardiovascular effects between smoked tobacco and cannabis using endothelial dysfunction as a measure
Description
We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked tobacco and cannabis.
Time Frame
Day 2 of each arm
Title
Puffing behaviors across all products
Description
We will examine how puffing behaviors are different between all products (smoked and vaped cannabis, as well as with smoked tobacco cigarettes) and how they correlate with toxicant biomarker concentrations. Vaping topography measures will be obtained from frame by frame analysis of high definition videos.
Time Frame
Days 1-2 of each arm

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy on the basis of medical history and limited physical examination, as described below: Heart rate < 105 beats per minute (BPM); Systolic Blood Pressure < 160 and > 90*; Diastolic Blood Pressure < 100 and > 50* *Considered out of range if both machine and manual readings are above/below these thresholds. Current regular user of cannabis who smokes cannabis as joint or blunt at least 3 times a week for past 3 months History of cannabis vaporizer use or willingness to use the vaporizer in the study Current tobacco cigarette use who smokes ≥ 5 cigarettes per day Saliva cotinine ≥ 50 ng/ml Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use Exclusion Criteria: Unstable medical conditions: Heart disease; Uncontrolled hypertension; Thyroid disease (okay if controlled with medication); Diabetes; Hepatitis B or C or Liver disease; Glaucoma; Prostatic hypertrophy Psychiatric conditions: Current or past schizophrenia, and/or current or past bipolar disorder; Adult onset attention deficit hyperactivity disorder (ADHD); Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion; History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval Concurrent regular use of smokeless tobacco or pipes [occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study] Medications: Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).; Concurrent use of nicotine-containing medications; Psychiatric medications: current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate. Other/Misc. Chronic Health Conditions: Oral thrush; Fainting; Untreated thyroid disease; Other "life threatening illnesses" as per study physician's discretion Pregnancy: Pregnancy (self-reported and urine pregnancy test); Breastfeeding (determined by self-report) Drug/Alcohol Dependence: Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program; Positive toxicology test at the screening visit (THC & prescribed medications okay); Methadone replacement therapy Concurrent participation in another clinical trial Inability to communicate in English History of marijuana-induced psychosis or paranoia after smoking marijuana Scoring a 2 or higher on the Severity of Dependence Scale for cannabis use Planning to quit smoking or vaping within the next 60 days
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Lawrence
Phone
(415) 608-4864
Email
Lisa.Lawrence@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gideon St. Helen, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zuckerberg San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Lawrence
Email
Lisa.Lawrence@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Armando Barraza
Email
Armando.Barraza@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Gideon St. Helen, PhD
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Lawrence
Phone
415-608-4864
Email
Lisa.Lawrence@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Armando Barraza
Email
armando.barraza@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Gideon St. Helen, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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THC Crossover Study

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