Gut Butyrate and Blood Pressure in African Americans

NCT04415333 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 18-1680
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

African Americans have the greatest burden of hypertension. Recently, the short-chain fatty acid, butyrate, has been reported to have some effect on blood pressure. Butyrate is not normally ingested since it is made by bacteria in the gut as a byproduct of fiber fermentation. In this proof of concept study, the investigators will investigate the effect of butyrate absorbed in the gut (via the participant self-administering an enema with butyrate) has on blood pressure.

Conditions

Hypertension

Keywords

African American; Blood pressure; Gut Microbiome; Short-chain fatty acid; Butyrate

Outcome Measures

Primary Outcomes (2)

• Mean Daytime Blood Pressure

  Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.

  approximately 16 hours post enema

• Mean Nighttime Blood Pressure

  Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.

  approximately 8 hours post enema

Secondary Outcomes (2)

• Blood Butyrate Concentrations

  up to 1 hour post enema

• Interleukin-1 Beta (IL-1β) Concentration

  up to 1 hour post enema

Study Arms (3)

Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]

EXPERIMENTAL

After a randomized assignment in the crossover design, participants with hypertension will come to the testing office to self-administer the first enema with a concentration of 5 mmol sodium butyrate in a 0.9% saline solution (60 mL total). After a 7-days washout period, they will return to testing office to self-administer the other enema with a concentration of 80 mmol sodium butyrate in a 0.9% saline solution (60 mL total).

Drug: Sodium Butyrate 5 mmol; Drug: Sodium Butyrate 80 mmol

Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]

EXPERIMENTAL

After a randomized assignment in the crossover design, participants with hypertension will come to the testing office to self-administer the first enema with a concentration of 80 mmol sodium butyrate in a 0.9% saline solution (60 mL total). After a 7-day washout period, they will return to the testing office to self-administer the other enema with a concentration of 5 mmol sodium butyrate in a 0.9% saline solution (60 mL total).

Drug: Sodium Butyrate 5 mmol; Drug: Sodium Butyrate 80 mmol

Control

NO INTERVENTION

African Americans with normal blood pressure (control group) will not perform self-administration of the enema. They will submit to 1 blood draw and wear the 24-hour ambulatory blood pressure monitor for 1-day.

Interventions

Sodium Butyrate 5 mmol DRUG

Enema-based delivery of 5 mmol butyrate in 0.9% saline, (60 mL total)

Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]; Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]

Sodium Butyrate 80 mmol DRUG

Enema-based delivery of 80 mmol butyrate in 0.9% saline, (60 mL total)

Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]; Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normotensive (control subjects without hypertension): In order to be eligible to participate in this study, an individual must meet all of the following criteria (which will be assessed after an initial telephone interview and at Visit 1 (screening and consent visit):
• Provision of signed and dated informed consent form
• Be an African American adult (man or woman) between 30 - 50 years of age with normal blood pressure (never diagnosed with hypertension) (systolic: 90-129 and diastolic: 60-89 mmHg).
• Body Mass Index of 18.5-30 kg/m\^2
• Not have any other diagnosed cardiovascular disease
• Not exercise regularly (Participate in less than 60 minutes of exercise/week)
• Not be pregnant or be lactating
• Be free of active diseases that affect your intestines (i.e., chronic constipation, diarrhea, Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, diabetes, hepatitis, HIV, and cancer)
• Have not taken antibiotics in the past 3 months
• Have not been regularly taking medications that impact intestinal function (i.e., laxatives, enemas, anti-diarrheal agents, narcotics, antacids, antispasmodics, antidepressants, anticonvulsants, antibiotics, herbals, homeopathy, and home remedies) or fiber supplements.
• Have no plans of travel out of town during the study periods.
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration
• Hypertension subjects not on anti-hypertension medication (intervention group). The pool of subjects that do not take hypertension medication may be limited. If a heavily medicated subject population is encountered, the investigators may include subjects taking diuretics only: In order to be eligible to participate in this study, an individual must meet all of the following criteria (which will be assessed after an initial telephone interview and at Visit 1 (screening and consent visit):
• Provision of signed and dated informed consent form. Letter of clearance or signature of PCP on informed consent.
• Be an African American adult (man or woman) between 30 - 50 years of age with stage-1 to stage-2 hypertension (systolic: 130-159 and diastolic: 80-99 mmHg).

You may not qualify if:

• Exercise more than 60 minutes per week for more than 4 consecutive weeks.
• Diagnosed with stroke, history of myocardial infarction (heart attack); liver, lung, or kidney diseases; peripheral vascular disease or cancer within the last 6 months.
• Presence of metabolic disease (diabetes mellitus), inflammatory diseases (e.g., inflammatory bowel diseases, rheumatoid arthritis, and systemic lupus erythematosus); kidney stones or gallbladder problems; diagnosed liver, lung or kidney diseases;
• Pregnancy, lactation, or actively trying to conceive.
• Taking anti-hypertension medications (i.e., calcium channel blockers, ACE inhibitors, angiotensin- receptor blockers, β-blockers, vasodilators, etc.) other than diuretics (e.g., hydrochlorothiazide, chlorothiazide, furosemide, etc) or medications known to affect inflammation or metabolic function (anti-inflammatories, statins, thyroid medication) in the past 1 month. If diuretics are used, subjects may able to participate if they agree to refrain from taking their diuretic the day of the experiment. In this instance, resting systolic BP while on their medication will still need to be greater than 130 mmHg.
• Current smoker or tobacco use within the last 10 years

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• North Carolina Translational and Clinical Sciences Institute: collaborator
• North Carolina Agriculture & Technical State University: collaborator

Study Sites (1)

NC A&T State University

Greensboro, North Carolina, 27411, United States

Location

Related Publications (5)

• Steinhart AH, Hiruki T, Brzezinski A, Baker JP. Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial. Aliment Pharmacol Ther. 1996 Oct;10(5):729-36. doi: 10.1046/j.1365-2036.1996.d01-509.x.

  PMID: 8899080 BACKGROUND

• Vanhoutvin SA, Troost FJ, Kilkens TO, Lindsey PJ, Hamer HM, Jonkers DM, Venema K, Brummer RJ. The effects of butyrate enemas on visceral perception in healthy volunteers. Neurogastroenterol Motil. 2009 Sep;21(9):952-e76. doi: 10.1111/j.1365-2982.2009.01324.x. Epub 2009 May 19.

  PMID: 19460106 BACKGROUND

• Hamer HM, Jonkers DM, Vanhoutvin SA, Troost FJ, Rijkers G, de Bruine A, Bast A, Venema K, Brummer RJ. Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission. Clin Nutr. 2010 Dec;29(6):738-44. doi: 10.1016/j.clnu.2010.04.002. Epub 2010 May 15.

  PMID: 20471725 BACKGROUND

• Krokowicz L, Stojcev Z, Kaczmarek BF, Kociemba W, Kaczmarek E, Walkowiak J, Krokowicz P, Drews M, Banasiewicz T. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis--a prospective randomized study. Int J Colorectal Dis. 2014 Mar;29(3):387-93. doi: 10.1007/s00384-013-1807-5. Epub 2013 Dec 18.

  PMID: 24343275 BACKGROUND

• Hogue T, Das P, Reczek S, Hampton-Marcell J, Ford Y, Raval D, Carroll I, Cook MD. Effect of Acute Gut Butyrate Delivery on Blood Pressure in Black Individuals With Hypertension: A Proof-of-Concept Randomized Controlled Study. J Am Heart Assoc. 2025 Sep 2;14(17):e039759. doi: 10.1161/JAHA.124.039759. Epub 2025 Jul 30.

  PMID: 40736085 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Butyric Acid

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Marc Cook, PhD
• Organization: North Carolina A&T State University

mdcook@ncat.edu

336-285-3547

Study Officials

• Marc D Cook, PhD

  North Carolina A&T State Univeristy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the participants with hypertension will perform the enema in a randomized order. The participants, nursing research staff (e.g., care providers), nor the PI's will know which enema the subjects are receiving. The study Biostatistician (e.g., statistical outcome assessor) will only be given the treatment IDs and not be given the sodium butyrate concentrations during statistical analyses. Randomization will be performed by 1 member of the research team at the beginning of the study who is also not involved in any informed consent process. Enemas will be assigned a letter (e.g., A or B) and each letter will be placed in an envelope (blinded allocation concealment). The research team member will reveal the key upon the conclusion of the study.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this blinded study, participants with Hypertension will self-administer a \[5 mmol\] and a \[80 mmol\] sodium butyrate enema in a randomized order 1 week (7 days) apart.

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: June 4, 2020
• Study Start: July 8, 2021
• Primary Completion: November 1, 2021
• Study Completion: November 2, 2021
• Last Updated: October 18, 2023
• Results First Posted: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: 3-5 years after the completion of the primary endpoint.
• Access Criteria: Contact Dr. Marc Cook (mdcook@ncat.edu) at NC A\&T State University. The data set will be shared in the Carolina Digital repository.

Locations

US (1)