Exercise Training Decreases Alcohol Consumption and Tissue Injury by an FGF21-dependent Mechanism
調査の概要
詳細な説明
Alcohol use disorder is a major driver of continued liver injury in alcohol-related liver disease. Patients with ALD also commonly develop sarcopenia, impaired skeletal muscle function, fatigue, mitochondrial dysfunction, reduced exercise capacity, and physical frailty. Exercise may improve muscle and metabolic function and may also reduce alcohol craving and consumption. FGF21 has been proposed as a mechanistic link among exercise, skeletal muscle, liver injury, metabolism, and alcohol-related behavior.
This is a randomized, controlled, unblinded study of 30 adults with AUD/ALD. Participants will be randomized 1:1 to endurance exercise plus standard of care (EE+SOC) or standard of care alone (SOC). Participants assigned to EE+SOC will complete a 12-week home-based supervised cycling program three days per week, with a target of approximately 60 minutes per session and intensity adjusted for safety, tolerance, and beta-blocker use. Exercise sessions will be remotely monitored, and fitness testing will occur at Cleveland Clinic. Participants in the SOC arm will continue usual clinical care and their usual physical activity without the structured exercise intervention.
The study will assess alcohol consumption and craving; circulating and skeletal muscle FGF21; liver injury measures; exercise capacity and physical performance; body composition; fatigue; skeletal muscle metabolism and mitochondrial function; and exploratory transcriptomic, proteomic, metabolomic, microbiome, amino acid, protein synthesis, TCA intermediate, and cell-signaling responses.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Annette Bellar, PhD
- 電話番号：216-445-6268
- メール：bellara@ccf.org
研究連絡先のバックアップ
- 名前：Research Coordinator
- 電話番号：216-445-6268
研究場所
-
-
Ohio
-
Cleveland、Ohio、アメリカ、44195
- 募集
- Cleveland Clinic
-
主任研究者：
- Srinivasan Dasarathy, MD
-
コンタクト：
- Annette Program Manager, PhD
- 電話番号：216-445-6268
- メール：bellara@ccf.org
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
• Adults age 18 years or older, of either sex.
- Clinical diagnosis of alcohol use disorder (AUD) / alcohol-related liver disease (ALD).
- Meets NIAAA hazardous-drinking criteria: at least 7 drinks/week for women or 14 drinks/week for men for more than 6 months, with ongoing alcohol use within 2 months of evaluation.
- MELD score less than 21.
- Able to safely participate in exercise testing and endurance exercise.
- Able to provide informed consent.
- No concurrent renal, cardiac, pulmonary, cerebrovascular, or malignant illness that affects skeletal muscle mass; no diabetes mellitus; and no use of medications that affect skeletal muscle mass/protein turnover as described in the protocol, including anabolic steroids, high-dose corticosteroids, or anticoagulants.
Exclusion Criteria:
• Pedal edema above the ankle or grade 2 pedal edema.
- Liver transplant.
- Active malignancy.
- Gastrointestinal bleed within the previous 4 weeks.
- Hepatic encephalopathy within the previous 6 months.
- Grade 2 or greater active esophageal varices.
- Active infection.
- Large ascites by clinical and/or imaging criteria.
- Advanced cardiac disease (NYHA class 3 or 4) or advanced pulmonary disease (GOLD class 3 or 4).
- Use of medications affecting muscle protein turnover, including corticosteroids, or medications used to prevent clotting.
- Prior orthopedic surgery or chronic joint pain that, in the opinion of the PI, may inhibit participation.
- INR greater than 1.7 or platelet count less than 60,000/mL.
- Unable to provide informed consent; judged likely to be unable to perform exercise or unlikely to complete the study in the opinion of the investigators.
- End-stage kidney disease defined as eGFR less than 15 mL/min/1.73 m² or dialysis.
- Considered unsafe for exercise in the opinion of the PI.
- Failure to pass the exercise stress test.
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：処理
- 割り当て：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 |
|---|---|
|
実験的：Endurance Exercise
Participants will receive standard of care and complete a 12-week supervised home-based endurance exercise program using a recumbent exercise bike.
|
Stationary/recumbent cycling three days per week for approximately 60 minutes per session for 12 weeks.
Exercise intensity is targeted at approximately 60-70% heart rate reserve and adjusted for safety, tolerance, and beta-blocker use.
Sessions are remotely monitored by the study team.
Participants who cannot exercise continuously may use rest breaks and complete the prescribed exercise within the limits described in the protocol.
|
|
介入なし：Standard of Care
Participants will continue usual clinical care and their current pattern of physical activity and will not participate in the structured endurance exercise intervention
|
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 |
|---|---|---|
|
Change in Alcohol Consumption Measured by Timeline Follow Back (TLFB)
時間枠：Baseline to 12 weeks
|
Alcohol consumption will be assessed using the Timeline Follow Back (TLFB).
The primary comparison is change over 12 weeks between the EE+SOC and SOC groups.
|
Baseline to 12 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Alcohol Cravings Measured by the Penn Alcohol Cravings Scale (PACS)
時間枠：Baseline to 12 weeks
|
Alcohol craving will be assessed using the Penn Alcohol Craving Scale (PACS).
The primary comparison is change over 12 weeks between the EE+SOC and SOC groups.
|
Baseline to 12 weeks
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Srinivasan Dasarathy, MD、The Cleveland Clinic
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
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。