Brain Dopamine Dynamics in Obesity (BDDO)
This study measures the brain's dopamine response to milkshake consumption in people with a healthy weight and people with obesity and examines whether this response differs between the two groups. Dopamine release will be measured using ultra-high-resolution positron emission tomography (PET) imaging with the NeuroEXPLORER scanner. The study will also examine how the dopamine response relates to hormonal responses measured at the same time and to participants' food intake behavior.
調査の概要
詳細な説明
This study aims to address three key questions: (1) whether the two phases of dopamine release in the striatum, a brain region involved in reward and motivation, during and after milkshake consumption differ between people with a healthy weight and people with obesity, and between men and women; (2) how metabolic and hormonal responses relate to dopamine release; and (3) whether dopamine-related networks outside the striatum differ between weight groups and predict eating behavior. These findings may improve our understanding of overeating and obesity and help inform the development of treatments that target the brain's dopamine system.
Each participant will complete four visits:
- Informed consent and screening to determine eligibility.
- A practice session to become familiar with PET scanning and the device used to deliver the milkshake.
- An MRI scan and assessments of eating behavior.
- A PET scan to measure dopamine release before and during milkshake delivery, with blood samples collected before and during the scan and questionnaires and tasks completed before and after the scan.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Elizabeth Sanchez Rangel, MD
- 電話番号：203-785-6430
- メール：elizabeth.sanchezrangel@yale.edu
研究連絡先のバックアップ
- 名前：Mireille Serlie, MD PhD
- 電話番号：2037375538
- メール：mireille.serlie@yale.edu
研究場所
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Connecticut
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New Haven、Connecticut、アメリカ、06520
- Yale 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
Inclusion Criteria:
- BMI 20-25 kg/m² (normal weight group) or BMI 30-45 kg/m² (obesity group)
- Stable body weight in the 3 months prior to enrollment (<5%weight change)
- Male sex or postmenopausal female (defined as cessation of menstrual periods for ≥12 consecutive months or FSH >25.8 mIU/mL)
- Able to read, write, and speak English
- Capable of giving informed consent
Exclusion Criteria:
- Premenopausal status in women
- Smoking (current use of any tobacco or nicotine products)
- History of or current psychiatric disorder
- History of or current neurological disorder
- History of bleeding disorder or use of anticoagulants
- History of or current eating disorder (Eating Disorder Examination Questionnaire)
- Presence of type 1 or type 2 diabetes mellitus
- Elevated liver enzymes (>2× the upper limit of normal)
- Renal insufficiency (eGFR <15 mL/min/1.73m²)
- Anemia and/or Hematocrit <35 vol%
- Uncontrolled thyroid disease
- Lactose intolerance
- Current use of systemic hormone therapy, including oral, transdermal, or injectable estrogen or combined estrogen-progestogen preparations
- Radiation exposure for research purposes within the past year such that participation in this study would place them over guideline limits for annual radiation exposure (an effective dose of 5 rem received per year).
- Current, past or anticipated exposure to radiation in the workplace within one year
- Presence of any somatic disorder or medication use that interferes with brain functional networks or metabolic response to food
- Shift work
- Current use of cannabis (any form), cocaine, amphetamines, or other recreational substances with known dopaminergic effects
- Heavy alcohol use, defined as >15 standard drinks per week for men or >8 standard drinks per week for women (National Institute on Alcohol Abuse and Alcoholism thresholds)
- Contraindications for MRI: metal implants incompatible with MRI, claustrophobia, large colored tattoos, or body weight >285 pounds
- Pacemaker in situ or other implanted electronic device
- Childhood-onset obesity (onset before age 10 years)
- Current or past (within last year prior to enrollment) pharmacological obesity treatment
- Past surgical obesity treatment (bariatric surgery)
- Current use of structured meal replacement programs
- Blood donation within 8 weeks prior to study
- Active oral or perioral conditions that may alter taste perception or compromise safety during gustometer use
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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実験的：Adults with obesity
Four visits per participant: screening, PET practice session, MRI+behavioral assessment, milkshake+PET scan. |
Strawberry, banana, chocolate, or vanilla flavored, delivered through a gustometer during the practice session and PET scan. A next-generation ultra-high-performance dedicated human brain PET scanner.
他の名前：
Carbon-11 radiolabeled PET ligand with high affinity and selectivity for postsynaptic dopamine receptors; one of the standard radiotracers for measuring dopamine release in humans.
他の名前：
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実験的：Adults with normal weight
Four visits per participant: screening, PET practice session, MRI+behavioral assessment, milkshake+PET scan. |
Strawberry, banana, chocolate, or vanilla flavored, delivered through a gustometer during the practice session and PET scan. A next-generation ultra-high-performance dedicated human brain PET scanner.
他の名前：
Carbon-11 radiolabeled PET ligand with high affinity and selectivity for postsynaptic dopamine receptors; one of the standard radiotracers for measuring dopamine release in humans.
他の名前：
|
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 |
|---|---|---|
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Dopamine (DA) release
時間枠：Visit 4, approximately week 4. Baseline D2/3R binding potential will be assessed at T=30'. PET time-activity curves are then measured continuously for 60 minutes from milkshake onset.
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Orosensory and post-ingestive DA release in the ventral and dorsal striatum during and after milkshake consumption |
Visit 4, approximately week 4. Baseline D2/3R binding potential will be assessed at T=30'. PET time-activity curves are then measured continuously for 60 minutes from milkshake onset.
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Time to onset of DA peaks
時間枠：Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
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Time to onset of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
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Duration of DA peaks
時間枠：Visit 4, approximately week 4.PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Duration of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4.PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Time to onset of DA peaks between men and women
時間枠：Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Time to onset of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Duration of DA peaks between men and women
時間枠：Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Duration of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Magnitude of DA release between men and women
時間枠：Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Magnitude of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
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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 |
|---|---|---|
|
Glucose
時間枠：Glucose will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
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To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Glucose will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
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Insulin
時間枠：Insulin will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Insulin will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
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FFA
時間枠：FFA will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
FFA will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
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Gut peptides (tbd)
時間枠：Gut peptides will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Gut peptides will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset.
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Yale Food Addiction Scale 2.0 score
時間枠：After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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Total score ranges from 0 to 11. Higher symptom counts indicate more symptoms of addictive-like eating. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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Barratt Impulsiveness Scale (BIS-11) score
時間枠：After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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A 30-item self-report questionnaire designed to measure human impulsiveness as a multidimensional personality and behavioral trait. Total score range 30 to 120, with higher scores reflecting greater impulsiveness. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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Dietary Fat and Free Sugar - Short Questionnaire (DFS)
時間枠：After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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A 26-item self-report tool to measure how often a person eats foods high in saturated fat and free sugar over the past 12 months. Total score range 26 to 130, with higher scores reflecting more frequent consumption of foods high in saturated fat and/or free sugars. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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Change in Delay Discounting Task
時間枠：The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=105' (duration of the task is 10 minutes)
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A behavioral assessment (computer task) to determine reward sensitivity (how much a person devalues a reward as the wait time for it increases). Calculated as Discount rate (k). Higher k indicates greater preference for immediate rewards. |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=105' (duration of the task is 10 minutes)
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Change in Iowa Gambling Task score
時間枠：The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=115' (duration of the task is 15 minutes)
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The Iowa Gambling Task is a behavioral task that assesses decision-making under uncertainty by asking participants to select cards from four decks with different rewards and losses. The net score is calculated by subtracting the number of selections from disadvantageous decks from the number of selections from advantageous decks. |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=115' (duration of the task is 15 minutes)
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Behavioral Inhibition System/Behavioral Activation System Scale score
時間枠：After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
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The Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales assess sensitivity to punishment and reward. The questionnaire contains 24 items, including 20 scored items and 4 filler items. It yields four subscale scores: Behavioral Inhibition (7-28), BAS Drive (4-16), BAS Fun Seeking (4-16), and BAS Reward Responsiveness (5-20). Higher scores indicate greater sensitivity to punishment, stronger pursuit of goals, greater fun seeking, and greater responsiveness to reward, respectively. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
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Change in Visual Analogue Scale (VAS) score
時間枠：The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=100' (duration of the task is 2 minutes)
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VAS to assess hunger and satiety on a scale of 0-100. Higher hunger scores indicate greater hunger, while higher satiety/fullness scores indicate greater satiety/fullness |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=100' (duration of the task is 2 minutes)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Mireille Serlie, MD PhD、Yale University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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
その他の研究ID番号
- 2000042630
- 1R01DK144194-01A1 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Computer codes developed for MRI and PET analysis will be shared on the open-access GitHub platform to support reproducibility. The study protocol and clinical data generated from this study will be uploaded to ClinicalTrials.gov. De-identified neuroimaging and research data will be submitted to appropriate NIH data repositories in compliance with NIH data sharing requirements.
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
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。