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SV2A Density Cannabis Use Disorder

Primary Purpose

Cannabis Use Disorder, Healthy

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
[11C]APP311
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cannabis Use Disorder focused on measuring Cannabis Use Disorder (CUD), Healthy subjects, synaptic vesicle density, [11C]APP311, UCB-J

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

CUD Participants Inclusion Criteria:

  1. Able to provide informed consent
  2. Male and female 18-75 years old
  3. Daily cannabis use
  4. Positive urine screen for cannabinoids and negative for all other drugs on
  5. Diagnosis of DSM-5 cannabis use disorder (≥ moderate, i.e., ≥ 4 [of 11] symptoms).
  6. Must express a willingness at screening to set a date to attempt to quit using cannabis.
  7. Physically healthy i.e., no clinically unstable medical conditions.
  8. For women of childbearing potential (WOCBP) and men, willingness to practice birth control and to inform study staff immediately if either they (for women) or their partner (for men) becomes pregnant.
  9. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

CUD Participants Exclusion Criteria:

  1. Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids.
  2. Women with a positive pregnancy test or women who are lactating.
  3. Have implanted or embedded metal objects or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field
  4. Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.
  5. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto) Subjects who have donated blood within 8 weeks of the present study
  6. Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
  7. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

Healthy Controls Inclusion Criteria:

  1. Willing and able to give voluntary written informed consent
  2. Male and Female subjects, age 18 to 75 years, inclusive
  3. BMI within 19 to 35 kg/m2, inclusive
  4. Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.
  5. Negative urine drug screen
  6. If female, not pregnant or breastfeeding
  7. If female of childbearing potential, must agree to use an acceptable method of birth control, as determined by the principal investigator, for the duration of the study and up to one month after completion of PET scans.
  8. Able to read and write, able to communicate effectively with the investigator, and comply with all study requirements, restrictions, and directions of the clinic staff.
  9. Have arterial access sufficient to allow blood sampling as per the protocol.

Healthy Controls Exclusion Criteria:

  1. History or presence of clinically significant and unstable respiratory, GI, renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers.
  2. Abnormal clinically significant laboratory or physical findings during screening
  3. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
  4. A condition that, in the opinion of the investigator, would prevent compliance with the study protocol.
  5. Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
  6. MRI incompatible implants and other contraindications for MRI, such as pace-maker, artificial joints, non-removable body piercings, metal fragments in head and/or body, or history working with ferrous metals either as a vocation or hobby in such a way that might have led to unknown, indwelling metal fragments that could cause injury during MRI etc.
  7. Subjects who suffer from claustrophobia.
  8. Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for healthy volunteers
  9. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

Sites / Locations

  • Yale University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

CUD Group

Healthy Controls

Arm Description

Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. CUD participants will be asked to abstain from cannabis for the 4 week period.

Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart.

Outcomes

Primary Outcome Measures

Hippocampal SV2A synaptic density
Hippocampal SV2A synaptic density will be measured using [11C]APP311 (UCB-J).

Secondary Outcome Measures

Hippocampal binding and Hippocampal Verbal Memory Task
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the hippocampal verbal memory task (Auditory Verbal Learning Task [AVLT]), a cognitive task that measures total immediate recall, before and after 4 weeks of confirmed cannabis abstinence.
Hippocampal binding and Groton Maze Learning in CUDs
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the Groton Maze Learning task, a cognitive task that measures total number of errors, in CUDs before and after 4 weeks of confirmed cannabis abstinence.

Full Information

First Posted
July 14, 2022
Last Updated
August 9, 2023
Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05472818
Brief Title
SV2A Density Cannabis Use Disorder
Official Title
SV2A Density Cannabis Use Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
May 2027 (Anticipated)
Study Completion Date
May 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

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

5. Study Description

Brief Summary
The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal [11C]APP-311/[11C]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed abstinence from cannabis, in comparison to healthy controls (HCs). Furthermore, any change in synaptic vesicle density will be placed in functional context by measuring verbal memory, which is sensitive to hippocampal function, before and after at least 4 weeks of confirmed abstinence. Finally, the relationship between hippocampal [11C]UCB-J binding in CUDs with measures of cannabis exposure (e.g., age of initiation, cumulative lifetime dose) will be explored.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cannabis Use Disorder, Healthy
Keywords
Cannabis Use Disorder (CUD), Healthy subjects, synaptic vesicle density, [11C]APP311, UCB-J

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
In this study, patients with cannabis use disorder (CUD) and matched healthy controls will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. CUD participants will be asked to abstain from cannabis for the 4 week period. A small subset of CUD participants will be asked to continue abstaining for an additional approx. 4 weeks to complete one additional scan. Participants may also complete a neurocognitive battery, various psychiatric evaluations, a physical examination, an ECG, blood tests, and questionnaires. CUD participants will complete bi-weekly study visits to confirm abstinence.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CUD Group
Arm Type
Active Comparator
Arm Description
Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. CUD participants will be asked to abstain from cannabis for the 4 week period.
Arm Title
Healthy Controls
Arm Type
Active Comparator
Arm Description
Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart.
Intervention Type
Drug
Intervention Name(s)
[11C]APP311
Intervention Description
For each [11C]APP311 (UCB-J) PET scan, up to 20 mCi of [11C]APP311 (UCB-J) will be administered by infusion pump. All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart. Approximately 8 CUD participants will be asked to return for a third [11C]APP311 (UCB-J) PET scan after an additional 4 weeks following their second scan.
Primary Outcome Measure Information:
Title
Hippocampal SV2A synaptic density
Description
Hippocampal SV2A synaptic density will be measured using [11C]APP311 (UCB-J).
Time Frame
All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.
Secondary Outcome Measure Information:
Title
Hippocampal binding and Hippocampal Verbal Memory Task
Description
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the hippocampal verbal memory task (Auditory Verbal Learning Task [AVLT]), a cognitive task that measures total immediate recall, before and after 4 weeks of confirmed cannabis abstinence.
Time Frame
The Auditory Verbal Learning Task (AVLT) will be administered before and after the 4 week abstinence period.
Title
Hippocampal binding and Groton Maze Learning in CUDs
Description
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the Groton Maze Learning task, a cognitive task that measures total number of errors, in CUDs before and after 4 weeks of confirmed cannabis abstinence.
Time Frame
The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.
Other Pre-specified Outcome Measures:
Title
Hippocampal synaptic density and first age of cannabis exposure
Description
To determine the relationship between hippocampal synaptic density (n=26+12 historical data) and indices of cannabis exposure such as first age of cannabis exposure, as measured by self-report data.
Time Frame
Before and after the 4 week abstinence period.
Title
Hippocampal synaptic density and cumulative lifetime cannabis exposure.
Description
To determine the relationship between hippocampal synaptic density (n=26+12 historical data) and indices of cannabis exposure such as cumulative lifetime cannabis exposure, as measured by self-report data.
Time Frame
Before and after the 4 week abstinence period.
Title
Hippocampal SV2A synaptic density after 8 weeks
Description
To explore whether hippocampal synaptic density and function continues to improve with 8 weeks of abstinence in a subset of CUD participants using [11C]APP311 (UCB-J).
Time Frame
Approximately 8 CUD participants will be asked to return for a third [11C]APP311 (UCB-J) PET scan after an additional 4 weeks following their second scan. (8 weeks in total).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
CUD Participants Inclusion Criteria: Able to provide informed consent Male and female 18-75 years old Daily cannabis use Positive urine screen for cannabinoids and negative for all other drugs on Diagnosis of DSM-5 cannabis use disorder (≥ moderate, i.e., ≥ 4 [of 11] symptoms). Must express a willingness at screening to set a date to attempt to quit using cannabis. Physically healthy i.e., no clinically unstable medical conditions. For women of childbearing potential (WOCBP) and men, willingness to practice birth control and to inform study staff immediately if either they (for women) or their partner (for men) becomes pregnant. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study. CUD Participants Exclusion Criteria: Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids. Women with a positive pregnancy test or women who are lactating. Have implanted or embedded metal objects or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto) Subjects who have donated blood within 8 weeks of the present study Medications that could alter synaptic density and, therefore, confound the interpretation of study data. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study. Healthy Controls Inclusion Criteria: Willing and able to give voluntary written informed consent Male and Female subjects, age 18 to 75 years, inclusive BMI within 19 to 35 kg/m2, inclusive Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests. Negative urine drug screen If female, not pregnant or breastfeeding If female of childbearing potential, must agree to use an acceptable method of birth control, as determined by the principal investigator, for the duration of the study and up to one month after completion of PET scans. Able to read and write, able to communicate effectively with the investigator, and comply with all study requirements, restrictions, and directions of the clinic staff. Have arterial access sufficient to allow blood sampling as per the protocol. Healthy Controls Exclusion Criteria: History or presence of clinically significant and unstable respiratory, GI, renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers. Abnormal clinically significant laboratory or physical findings during screening History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto) A condition that, in the opinion of the investigator, would prevent compliance with the study protocol. Medications that could alter synaptic density and, therefore, confound the interpretation of study data. MRI incompatible implants and other contraindications for MRI, such as pace-maker, artificial joints, non-removable body piercings, metal fragments in head and/or body, or history working with ferrous metals either as a vocation or hobby in such a way that might have led to unknown, indwelling metal fragments that could cause injury during MRI etc. Subjects who suffer from claustrophobia. Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for healthy volunteers Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kayla Cottiers, B.S.
Phone
203-974-7544
Email
kayla.cottiers@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kelly Daniels, B.A.
Phone
(203) 932-5711
Ext
5768
Email
kelly.daniels@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deepak C D'Souza
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

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SV2A Density Cannabis Use Disorder

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