SV2A 密度大麻使用障害
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.
調査の概要
研究の種類
入学 (実際)
段階
- 初期フェーズ 1
連絡先と場所
研究場所
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Connecticut
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New Haven、Connecticut、アメリカ、06511
- Yale University School of Medicine
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:基礎科学
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ:CUD Group
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. |
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. |
|
アクティブコンパレータ:Healthy Controls
Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. |
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. |
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Hippocampal SV2A synaptic density
時間枠:All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.
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Hippocampal SV2A synaptic density will be measured using [11C]APP311 (UCB-J). |
All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Hippocampal binding and Hippocampal Verbal Memory Task
時間枠:The Auditory Verbal Learning Task (AVLT) will be administered before and after the 4 week abstinence period.
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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. |
The Auditory Verbal Learning Task (AVLT) will be administered before and after the 4 week abstinence period.
|
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Hippocampal binding and Groton Maze Learning in CUDs
時間枠:The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.
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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. |
The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Hippocampal synaptic density and first age of cannabis exposure
時間枠:Before and after the 4 week abstinence period.
|
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. |
Before and after the 4 week abstinence period.
|
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Hippocampal synaptic density and cumulative lifetime cannabis exposure.
時間枠:Before and after the 4 week abstinence period.
|
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. |
Before and after the 4 week abstinence period.
|
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Hippocampal SV2A synaptic density after 8 weeks
時間枠: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).
|
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). |
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).
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Deepak C D'Souza、Yale University
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- 2000032181
- 1R01DA054314 (米国 NIH グラント/契約)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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