Effectiveness of a Butyrate Formulation and Butyrate + Polyphenol Formulation on Gut Health, Permeability and Associated Symptoms

Gut Health Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of a Butyrate Formulation and a Butyrate + Polyphenol Formulation on Gut Health, Permeability and Associated Symptoms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06419231
• Other study ID #: CL115
• Status: Recruiting
• Phase: N/A
• Start date: October 31, 2023
• Est. completion date: February 21, 2025

Study information

• Verified date: May 2024
• Source: Supplement Formulators, Inc.
• Contact: Steven Hirsh, RPh, DPM
• Phone: 954-202-7679
• Email: shirsh[@]lifeextension.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is the assess the effectiveness and safety of a Butyrate formulation and a Butyrate + Polyphenol formulation on gut health, permeability and associated symptoms

Description:

This is a double-blind, randomized, placebo-controlled, remote design study to evaluate the effects of a Butyrate formulation and Butyrate + Polyphenol formulation on gut health, intestinal permeability and associated symptoms.

Participants will be asked to complete laboratory assessments and questionnaires. A total of up to 105 subjects (35 subjects per arm) will be enrolled in a randomly assigned sequence for the 28-day period. There will be three scheduled remote videoconferencing visits with two scheduled telephone contacts. The study subjects will complete assessment tools that include the Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS), Digestion-Associated Quality of Life Questionnaire (DQLQ), Visual Abdominal Scale of Abdominal Pain, Bristol Stool Form (BSFS), Gastrointestinal-Global Assessment of Improvement (Gastrointestinal-GAI) and the Short Form-36 Health Survey (SF-36). Laboratory testing will include Gut Microbiome, Short Chain Fatty Acid Analysis, Gut Barrier Panel and Intestinal Permeability.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: February 21, 2025
• Est. primary completion date: January 24, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Ambulatory, male or female, 21-70 years of age

2. A BMI of 18.5-34.9

3. Experiences at least three of the following conditions on a weekly basis (gastrointestinal discomfort, abdominal pain, gas, bloating, diarrhea or constipation)

4. Are comfortable fasting overnight

5. Are able to complete study procedures for up to approximately 6 hours on 2 separate days

6. Considered to be generally healthy on the basis of medical history

7. Willing to follow study instructions, including compliance with the study procedures and requirements

Exclusion Criteria:

1. Unable to provide a urine specimen, stool specimen or blood sample from a finger stick

2. Currently on a galactose/lactose restricted diet

3. Having taken proton pump inhibitors (e.g. omeprazole, pantoprazole) within the past 3 months

4. History of oral antibiotic use within the past 3 months

5. Current or previous history of gastrointestinal disease including gallbladder problems, gallstones, biliary obstruction, irritable bowel disease (IBD) or that may interfere with the outcome parameters

6. Current or previous history of gastrointestinal cancer

7. Currently experience or have had a gastrointestinal infection (virus or bacterial) or food poisoning within the past month

8. Currently experience or have had a parasitic infection within the past 3 months

9. Currently experience or have a history of Crohn's disease, colitis, or celiac disease

10. Currently experience or have a history of severe endometriosis

11. History of gastrointestinal surgery which might influence gastrointestinal function except appendectomy or cholecystectomy

12. .History of thyroid disease (except on a stable dose of medication for = 3 months before screening and unlikely to change medication or dose during the study)

13. History of hypertension (except on a stable dose of medication for = 3 months before screening and unlikely to change medication or dose during the study)

14. A medical or surgical event requiring hospitalization, outpatient visits or emergency room visits within the past 5 years or in the judgment of the Study Investigator /Sub-I would preclude participation in the study

15. Current or previous history of diabetes

16. History of a major change in dietary habits with the past 1 month

17. History of cancer (including skin cancer) within the past 5 years

18. Known intolerance or allergy to sugar alcohols including mannitol, sorbitol, xylitol, lactulose or lactose

19. Women who are lactating, pregnant or planning pregnancy within the next two months

20. Women who are currently taking or have taken estrogen and/or progesterone as a method of birth control < 3 months prior to screening or anticipates a change for the duration of the study period

21. Having donated blood or received a blood transfusion within 30 days before screening

22. Currently participating in another clinical research study or participated in another clinical research study within 30 days prior to screening

Related Conditions & MeSH terms

• Gut Health

Intervention

Dietary Supplement:
• Butyrate Formulation
Butyrate Formulation capsule:3 capsules daily
• Butyrate + Polyphenol Formulation
Butyrate + Polyphenol Formulation capsule: 3 capsules daily
• Placebo
Placebo: 3 capsules daily

Locations

Country	Name	City	State
United States	Life Extension Clinical Research, Inc.	Fort Lauderdale	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Supplement Formulators, Inc.	Compound Solutions Inc.

Country where clinical trial is conducted

United States, 

References & Publications (25)

Asbaghi O, Nazarian B, Reiner Z, Amirani E, Kolahdooz F, Chamani M, Asemi Z. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2020 Feb;34(2):239-253. doi: 10.1002/ptr.6518. Epub 2019 Dec 26. Erratum In: Phytother Res. 2022 Mar;36(3):1413. — View Citation

Banasiewicz T, Krokowicz L, Stojcev Z, Kaczmarek BF, Kaczmarek E, Maik J, Marciniak R, Krokowicz P, Walkowiak J, Drews M. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis. 2013 Feb;15(2):204-9. doi: 10.1111/j.1463-1318.2012.03152.x. — View Citation

Brooker S, Martin S, Pearson A, Bagchi D, Earl J, Gothard L, Hall E, Porter L, Yarnold J. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiother Oncol. 2006 Apr;79(1):45-51. doi: 10.1016/j.radonc.2006.02.008. Epub 2006 Mar 20. — View Citation

Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011 Mar 28;17(12):1519-28. doi: 10.3748/wjg.v17.i12.1519. — View Citation

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. — View Citation

Conley BA, Egorin MJ, Tait N, Rosen DM, Sausville EA, Dover G, Fram RJ, Van Echo DA. Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. Clin Cancer Res. 1998 Mar;4(3):629-34. — View Citation

Cory H, Passarelli S, Szeto J, Tamez M, Mattei J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front Nutr. 2018 Sep 21;5:87. doi: 10.3389/fnut.2018.00087. eCollection 2018. — View Citation

Costa C, Tsatsakis A, Mamoulakis C, Teodoro M, Briguglio G, Caruso E, Tsoukalas D, Margina D, Dardiotis E, Kouretas D, Fenga C. Current evidence on the effect of dietary polyphenols intake on chronic diseases. Food Chem Toxicol. 2017 Dec;110:286-299. doi: 10.1016/j.fct.2017.10.023. Epub 2017 Oct 14. — View Citation

Dallal, G. (2021). www.Randomization.com. http://www.randomization.com

Drugs, O. o. N. (2005). Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Office of the Federal Register National Archives and Record Administration

Edelman MJ, Bauer K, Khanwani S, Tait N, Trepel J, Karp J, Nemieboka N, Chung EJ, Van Echo D. Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug. Cancer Chemother Pharmacol. 2003 May;51(5):439-44. doi: 10.1007/s00280-003-0580-5. Epub 2003 Mar 12. — View Citation

Grosicki, G. (2021). Effects of 3-week Tributyrin Supplementation on the Gut Microbiome: A Pilot Study. Journal of the Academy of Nutrition and Dietetics, 121(9, Supplement), A23. https://doi.org/https://doi.org/10.1016/j.jand.2021.06.051

Hodges, J., Zeng, M., Cao, S., Pokala, A., Rezaei, S., Sasaki, G., Vodovotz, Y., & Bruno, R. (2022). Catechin-Rich Green Tea Extract Reduced Intestinal Inflammation and Fasting Glucose in Metabolic Syndrome and Healthy Adults: A Randomized, Controlled, Crossover Trial. Current Developments in Nutrition, 6(Supplement_1), 981-981. https://doi.org/10.1093/cdn/nzac068.010

Hodgkinson K, El Abbar F, Dobranowski P, Manoogian J, Butcher J, Figeys D, Mack D, Stintzi A. Butyrate's role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr. 2023 Feb;42(2):61-75. doi: 10.1016/j.clnu.2022.10.024. Epub 2022 Nov 2. — View Citation

Istas G, Wood E, Le Sayec M, Rawlings C, Yoon J, Dandavate V, Cera D, Rampelli S, Costabile A, Fromentin E, Rodriguez-Mateos A. Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men. Am J Clin Nutr. 2019 Aug 1;110(2):316-329. doi: 10.1093/ajcn/nqz075. — View Citation

Kapolou, A., Karantonis, H. C., Rigopoulos, N., & Koutelidakis, A. E. (2021). Association of Mean Daily Polyphenols Intake with Mediterranean Diet Adherence and Anthropometric Indices in Healthy Greek Adults: A Retrospective Study. Applied Sciences, 11(10), 4664. https://www.mdpi.com/2076-3417/11/10/4664

Le Sayec M, Xu Y, Laiola M, Gallego FA, Katsikioti D, Durbidge C, Kivisild U, Armes S, Lecomte M, Fanca-Berthon P, Fromentin E, Plaza Onate F, Cruickshank JK, Rodriguez-Mateos A. The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial. Clin Nutr. 2022 Nov;41(11):2549-2561. doi: 10.1016/j.clnu.2022.08.024. Epub 2022 Sep 6. — View Citation

Ljotsson B, Jones M, Talley NJ, Kjellstrom L, Agreus L, Andreasson A. Discriminant and convergent validity of the GSRS-IBS symptom severity measure for irritable bowel syndrome: A population study. United European Gastroenterol J. 2020 Apr;8(3):284-292. doi: 10.1177/2050640619900577. Epub 2020 Jan 14. — View Citation

Ma, G., & Chen, Y. (2020). Polyphenol supplementation benefits human health via gut microbiota: A systematic review via meta-analysis. Journal of Functional Foods, 66, 103829. https://doi.org/https://doi.org/10.1016/j.jff.2020.103829

Park SY, Kim YD, Kim MS, Kim KT, Kim JY. Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial. Food Funct. 2023 Feb 6;14(3):1520-1529. doi: 10.1039/d2fo01835g. — View Citation

Pietrzak A, Banasiuk M, Szczepanik M, Borys-Iwanicka A, Pytrus T, Walkowiak J, Banaszkiewicz A. Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial. Nutrients. 2022 Aug 11;14(16):3283. doi: 10.3390/nu14163283. — View Citation

Recharla N, Geesala R, Shi XZ. Gut Microbial Metabolite Butyrate and Its Therapeutic Role in Inflammatory Bowel Disease: A Literature Review. Nutrients. 2023 May 11;15(10):2275. doi: 10.3390/nu15102275. — View Citation

Rosner, B. (2006). Hypothesis Testing Two-Sample Inference. In Fundamentals of Biostatistics (6th ed., pp. 331-334). Duxbury Press.

Wang X, Qi Y, Zheng H. Dietary Polyphenol, Gut Microbiota, and Health Benefits. Antioxidants (Basel). 2022 Jun 20;11(6):1212. doi: 10.3390/antiox11061212. — View Citation

Zhang H, Liu S, Li L, Liu S, Liu S, Mi J, Tian G. The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials. Medicine (Baltimore). 2016 Aug;95(33):e4247. doi: 10.1097/MD.0000000000004247. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut Microbiome	Assessment of the median change in the Gut Microbiome from baseline.	28 days
Primary	Gastrointestinal Symptom Rating Scale- IBS (GSRS-IBS)	Assessment of the median change in the Gastrointestinal Symptom Rating Scale-IBS from baseline.	28 days
Secondary	Gut Barrier Panel Finger Stick Test	Assessment of the median change in the Gut Barrier Panel Finger Stick Test from baseline.	28 days
Secondary	Short Chain Fatty Acid Analysis (SCFA)	Assessment of the median change in the Short Chain Fatty Acid Analysis from baseline.	28 days
Secondary	Intestinal Permeability Test (IP)	Assessment of the median change in the Intestinal Permeability Test from baseline.	28 days
Secondary	Digestive Quality of Life Questionnaire (DQLQ)	Assessment of the median change in the Digestive Quality of Life Questionnaire from baseline.	28 days
Secondary	Visual Analogue Scale questionnaire of abdominal pain	Assessment of the median change in the Visual Analogue Scale Questionnaire of abdominal pain from baseline.	28 days
Secondary	Bristol Stool Form (BSFS)	Assessment of the median change in the Bristol Stool Form from baseline.	28 days
Secondary	Gastrointestinal- global assessment of improvement scales (Gastrointestinal- GAI)	Assessment of the median change in the Gastrointestinal- global assessment of improvement scale from baseline.	28 days
Secondary	Short Form-36 Health Survey (SF-36 Health Survey)	Assessment of the median change in the SF-36 Health Survey from baseline	28 days