Effect of Oral Calcium Butyrate Supplementation in Obesity (Pacayeliztli)
Effect of Oral Calcium Butyrate Supplementation on Monocyte Mitochondrial Function and Gut Microbiota in Adults With Obesity
Obesity is characterized by gut microbiota dysbiosis, in which beneficial metabolites such as butyrate are reduced. Butyrate is a short-chain fatty acid produced by microbial fermentation that plays a key role in maintaining intestinal barrier integrity, regulating immune responses, and supporting mitochondrial function. Its depletion contributes to disruption of the intestinal barrier, facilitating the translocation of bacterial components and promoting systemic inflammation mediated by immune cell activation, like monocytes. This chronic inflammatory state is associated with mitochondrial dysfunction and impaired cellular bioenergetics. Butyrate has been investigated for its anti-inflammatory and metabolic effects, however, its direct impact on monocyte mitochondrial function and its relationship with gut microbiota composition in humans remains unclear.
This randomized, double-blind, placebo-controlled trial will evaluate the effect of oral calcium butyrate supplementation (1000 mg/day) compared with placebo for 4 weeks in adults with obesity. The primary objective is to determine the change in monocyte mitochondrial maximal respiration baseline to week 4.
調査の概要
詳細な説明
The study will consist of a screening phase (pre-admission) and two visits, followed by asynchronous follow-up.
Pre-admission visit Participants meeting inclusion criteria (presence of obesity) will be recruited through advertisements published on official institutional platforms.
Informed consent will be explained and signed prior to any study-related procedures.
Participants will be informed about the study characteristics, procedures, risks, and expected benefits, including dietary intervention and biochemical assessments.
A clinical history will be obtained, including identification data, contact information, medical history, and current or recent use of medications and supplements.
Anthropometric measurements (weight and height) will be obtained for BMI calculation.
Blood pressure will be measured after at least 5 minutes of rest, with two readings per arm separated by 3 minutes and averaged.
A blood sample will be collected to determine glucose, creatinine, and liver function tests.
Eligible participants will receive a stool collection kit with instructions for microbiota analysis and will be instructed to return the sample at the next visit.
Visit 1: Baseline Anthropometric measurements will be recorded (weight, height, waist circumference).
Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function.
The stool sample collected will be received for microbiota and short-chain fatty acids analysis.
Intervention Participants will be randomly assigned to either: Butyrate supplement group, or placebo group. An isocaloric maintenance diet will be prescribed (50% carbohydrates, 20% protein, 30% fat, 25 g/day fiber), including menus and food lists. Study capsules will be provided along with: Instructions for administration, adherence logbook, identification of adverse event monitoring (nausea, vomiting, abdominal discomfort, diarrhea, constipation, headache, dizziness, fatigue)
Visit 2: Final (After 4 weeks of intervention) Nutritional and Clinical Assessment Anthropometric measurements will be recorded (weight, height, waist circumference).
Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function and mitochondrial function.
The stool sample collected will be received for microbiota and short-chain fatty acids analysis.
Capsule count and adherence log review will be conducted. The adverse events questionnaire will be administered.
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：Martha Guevara, MD, PhD
- 電話番号：2802 +52 55 5487 0900
- メール：martha.guevarac@incmnsz.mx
研究連絡先のバックアップ
- 名前：Lilia Noriega, PhD
- 電話番号：2802 +52 55 5487 0900
- メール：lilia.noriegal@incmnsz.mx
研究場所
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Mexico City
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Mexico City、Mexico City、メキシコ、14080
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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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:
- Signing of the informed consent form.
- Adults aged ≥18 years of age.
- Body mass index (BMI) >30 kg/m².
- Both sex
Exclusion Criteria:
- Diabetes mellitus, defined as fasting glucose >126 mg/dL during screening.
- Hypertension, defined as blood pressure ≥130/80 mmHg during screening.
- Chronic kidney disease or estimated glomerular filtration rate <60 mL/min/1.73 m².
- Known liver disease.
- Secondary causes of obesity or diabetes, including Cushing syndrome, clinical or subclinical hypothyroidism, or pheochromocytoma.
- Catabolic diseases such as cancer or acquired immunodeficiency syndrome.
Drug treatment:
- Antihypertensive drugs or treatment (thiacycline, loop or potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, alpha blockers, calcium antagonists, beta blockers).
- Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or insulin and antidiabetic drugs.
- Treatment with statins, fibrates or other drugs to control dyslipidemia.
- Use of antibiotics in the three months prior to the study.
- Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
- Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
- Supplements with any of the functional foods used in the study.
- Probiotic, prebiotic or symbiotic supplements.
- Chronic proton pump inhibitor use or use within the last 2 weeks.
- Chronic use of laxatives, antispasmodics, or medications affecting intestinal motility.
- Current tobacco use.
- Daily alcohol consumption >1 drink/day during the last month.
- Use of recreational psychoactive substances.
- Pregnancy or lactation.
- Bariatric surgery or participation in intensive weight loss programs.
- Weight loss ≥3 kg in less than 3 months.
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：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：Placebo
Participants will receive oral placebo capsules containing maltodextrin at a dose of 600 mg/day, administered as two 300 mg capsules once daily for 4 weeks.
Furthermore, the participants will follow the same standardized isocaloric maintenance diet (50% carbohydrates, 20% protein, 30% fat) throughout the study.
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Oral placebo capsules containing maltodextrin, 300 mg per capsule.
Participants assigned to the placebo comparator arm will take two capsules once daily, for a total dose of 600 mg/day, for 4 weeks.
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実験的：Butyrate
Participants will receive calcium butyrate capsules at a dose of 1000 mg/day (2 capsules of 500 mg) by oral administration once daily for 4 weeks.
Furthermore, the participants will follow the same standardized isocaloric maintenance diet (50% carbohydrates, 20% protein, 30% fat) throughout the study.
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Oral calcium butyrate capsules, 500 mg per capsule.
Participants assigned to the experimental arm will take two capsules once daily, for a total dose of 1000 mg/day, for 4 weeks.
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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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Monocyte mitochondrial maximal respiration in pmol O₂/min/10⁶
時間枠：From baseline to week 4 of the intervention
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Change in maximal respiration measured in Cluster of differentiation 14 (CD14+) monocytes using extracellular flux mitochondrial stress testing.
Maximal respiration will be calculated as peak oxygen consumption rate (OCR) after Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) stimulation minus non-mitochondrial respiration, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Gut microbiota composition as relative abundance percentage
時間枠：From baseline to week 4 of the intervention
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Changes in gut microbiota composition will be assessed by 16 svedberg unit (16S) ribonucleic acid ribosomal (rRNA) sequencing, including alpha diversity (Chao1, Shannon), beta diversity, and relative taxonomic.
and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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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 |
|---|---|---|
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Monocyte mitochondrial reserve respiratory capacity in pmol O₂/min/10⁶ cells
時間枠：From baseline to week 4 of the intervention
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Change in reserve respiratory capacity measured in CD14+ monocytes using extracellular flux mitochondrial stress testing, will be calculated as the difference between maximal oxygen consumption rate and basal oxygen consumption rate, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Monocyte Bioenergetic Health Index (BHI) score
時間枠：From baseline to week 4 of the intervention
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Change in Bioenergetic Health Index measured in CD14+ monocytes using extracellular flux mitochondrial stress test.
BHI will be calculated as (ATP-linked respiration × spare respiratory capacity) / (proton leak × non-mitochondrial respiration), and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Fecal butyrate concentration in µmol/g
時間枠：From baseline to 4 week of the intervention
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Change in fecal butyrate concentration measured in stool samples by gas chromatography, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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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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Body mass index in kg/m²
時間枠：From baseline to 4 week of the intervention
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Change in body mass index calculated as weight in kilograms divided by height in meters squared, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Skeletal muscle mass percentage
時間枠：From baseline to 4 week of the intervention
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Change in skeletal muscle mass measured by bioimpedance, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Waist circumference in centimeter
時間枠：From baseline to 4 week of the intervention
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Change in waist circumference measured at the midpoint between the lower costal margin and the iliac crest at the end of a normal expiration, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Lean body mass percentage
時間枠：From baseline to 4 week of the intervention
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Change in lean body mass measured by bioimpedance, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Fat body mass percentage
時間枠：From baseline to week 4 of the intervention
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Change in fat mass percentage measured by bioimpedance, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Body weight in kilograms
時間枠：From baseline to week 4 of the intervention
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Change in body weight measured using a calibrated scale under fasting conditions and light clothing, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Systolic and diastolic blood pressure in mmHg
時間枠：From baseline to 4 week of the intervention
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Change in systolic and diastolic blood pressure with an appropriately sized cuff, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Serum glucose concentration in mg/dL
時間枠：From baseline to week 4 of the intervention
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Changes in the concentration of serum glucose measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Total cholesterol serum concentration in mg/dL
時間枠：From baseline to week 4 of the intervention
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Changes in total cholesterol concentrations measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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High-density lipoprotein cholesterol serum concentration in mg/dL
時間枠：From baseline to week 4 of the intervention
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Changes in H igh-density lipoprotein cholesterol concentrations measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Serum alanine aminotransferase concentration in IU/mL
時間枠：From baseline to 4 week of the intervention
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Changes in Serum alanine aminotransferase measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Serum aspartate aminotransferase concentration in IU/mL
時間枠：From baseline to week 4 of the intervention
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Change in serum aspartate aminotransferase measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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Serum high-sensitivity C-reactive protein concentration in mg/dL
時間枠：From baseline to 4 week of the intervention
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Changes in high-sensitivity C-reactive protein determined by autoanalyzer, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Serum interleukin-6 (IL-6) concentration in pg/mL
時間枠：From baseline to 4 week of the intervention
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Changes in IL-6 concentrations measured by enzyme-linked immunosorbent assay, and compared between the intervention and placebo groups.
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From baseline to 4 week of the intervention
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Low-density lipoprotein cholesterol serum concentration in mg/dL
時間枠：From baseline to week 4 of the intervention
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Changes in High-density lipoprotein cholesterol concentrations measured by automated analyzer, and compared between the intervention and placebo groups.
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From baseline to week 4 of the intervention
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協力者と研究者
捜査官
- スタディディレクター：Martha Guevara, PhD、Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
出版物と役立つリンク
一般刊行物
- Cleophas MCP, Ratter JM, Bekkering S, Quintin J, Schraa K, Stroes ES, Netea MG, Joosten LAB. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci Rep. 2019 Jan 28;9(1):775. doi: 10.1038/s41598-018-37246-7.
- Guevara-Cruz M, Hernandez-Gomez KG, Condado-Huerta C, Gonzalez-Salazar LE, Pena-Flores AK, Pichardo-Ontiveros E, Serralde-Zuniga AE, Sanchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, Lopez-Barradas A, Rodriguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velazquez-Villegas LA. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clin Nutr. 2024 Aug;43(8):1914-1928. doi: 10.1016/j.clnu.2024.06.036. Epub 2024 Jul 5.
- Borja-Magno AI, Furuzawa-Carballeda J, Guevara-Cruz M, Arias C, Granados J, Bourges H, Tovar AR, Sears B, Noriega LG, Gomez FE. Supplementation with EPA and DHA omega-3 fatty acids improves peripheral immune cell mitochondrial dysfunction and inflammation in subjects with obesity. J Nutr Biochem. 2023 Oct;120:109415. doi: 10.1016/j.jnutbio.2023.109415. Epub 2023 Jul 10.
- Marino F, Petrella L, Cimmino F, Pizzella A, Monda A, Allocca S, Rotondo R, D'Angelo M, Musco N, Iommelli P, Catapano A, Bagnato C, Paolini B, Cavaliere G. From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System. Biomolecules. 2025 Apr 29;15(5):638. doi: 10.3390/biom15050638.
- Guo Y, Shao M, Guan P, Yu M, Geng L, Gao Y, Meng L, Qu B. Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins. Plants (Basel). 2024 Jun 30;13(13):1807. doi: 10.3390/plants13131807.
- Kalkan AE, BinMowyna MN, Raposo A, Ahmad MF, Ahmed F, Otayf AY, Carrascosa C, Saraiva A, Karav S. Beyond the Gut: Unveiling Butyrate's Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review. Nutrients. 2025 Apr 9;17(8):1305. doi: 10.3390/nu17081305.
- Coppola S, Avagliano C, Calignano A, Berni Canani R. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021 Jan 28;26(3):682. doi: 10.3390/molecules26030682.
- Coppola S, Nocerino R, Paparo L, Bedogni G, Calignano A, Di Scala C, de Giovanni di Santa Severina AF, De Filippis F, Ercolini D, Berni Canani R. Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2244912. doi: 10.1001/jamanetworkopen.2022.44912.
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。
Placeboの臨床試験
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Shanghai Hengrui Pharmaceutical Co., Ltd.完了
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