Gut Butyrate and Blood Pressure in African Americans

Hypertension Clinical Trial

Official title:

Effect of Gut Butyrate Delivery on Blood Pressure in African Americans With Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04415333
• Other study ID #: 18-1680
• Status: Completed
• Phase: Phase 1
• Start date: July 8, 2021
• Est. completion date: November 2, 2021

Study information

• Verified date: October 2023
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Description: African Americans (AA) have the greatest burden of hypertension. Recently, gut microbial dysbiosis (a term that describes a poorly diverse gut microbial profile and lower short-chain fatty acid (SCFA) production) has been linked to hypertension and may be involved in the pathogenesis of hypertension in African Americans. African Americans have been reported to have lower gut SCFA and SCFA can reduce blood pressure. This is a proof of concept pilot study to determine the relationship between gut SCFA and blood pressure (BP). Delivery of butyrate to the gut will be via enema.

Objectives: The objectives of this research are to 1. Identify gut microbial taxa (SCFA butyrate-producing microbes) and circulating butyrate levels associated with hypertension via a cross-sectional design in AA without and with hypertension. 2. Quantify the relationship between SCFA (butyrate) absorption into the bloodstream and subsequent changes in blood pressure in a 24-hour period after delivering butyrate into the gut via enema.

Participants: African Americans males and females ages of 30-50 without hypertension (normal BP/healthy control; systolic BP: 90-129/ diastolic BP: 60-89mmHg) and with hypertension (systolic BP: 130-159 mmHg/ diastolic BP: 80-99 mmHg) that do not take anti-hypertension medication will be recruited.

Description of Study: There are 2 groups; control (without hypertension; BP:

90-129/60-89mmHg; 5 male/5 female, n=10) and experimental (with hypertension; BP 130-159/80-99 mmHg; 5 male/5 female, n=10). Normotensive participants (control group) will be age (±1 year) and sex-matched to hypertensive group participants. All participants (control and experimental groups; 5 male/5 female) will provide stool and blood samples, and complete 24-hour (hr) ambulatory blood pressure (ABP) monitoring to compare the abundance of fecal butyrate-producing microbes, circulating (blood) butyrate concentrations, and average blood pressure responses during the day and overnight. Individuals in the control group will only participate in donating stool (1-time) and a blood sample (1-time) and wearing a 24-hr ABP monitor (1-day). In a crossover blinded randomized controlled pilot study, the 10 hypertensive AA subjects (5 male/5 female) will be randomized to self-administer a sodium butyrate (80mmol butyrate in 0.9% saline, 60 ml total) or control (low dose) butyrate (5mmol butyrate 0.9%, 60 ml total) enema 1 week apart (7 days). Subjects will provide a stool sample before each study day (2 total), have their BP measured via ABP monitor, submit to a blood draws (pre-enema-baseline), self-administer the randomized enema, submit to a 30 min & 60 min post-enema blood draw, and wear the 24-hour ABP monitor for the remainder of that day. Subjects will be provided with written and verbal instructions on how to self-administer the enema. The dietary supplement (sodium butyrate) will be compounded by a local pharmacy (Custom Care Pharmacy - 109 Pisgah Church Rd. Greensboro, NC) into an enema at the concentrations listed above.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 50 Years

Eligibility

Inclusion Criteria:

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).

• Not taking any anti-hypertension medications (although the investigators may enroll individuals only taking a diuretic where resting BP levels are within the range of stage-1 hypertension: systolic BP 130-140 mmHg. Subjects can resume taking the diuretic after they remove the monitor).

• 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, diuretics, 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 throughout study duration

Exclusion Criteria for both groups:

• 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, ß-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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Sodium Butyrate 5 mmol
Enema-based delivery of 5 mmol butyrate in 0.9% saline, (60 mL total)
• Sodium Butyrate 80 mmol
Enema-based delivery of 80 mmol butyrate in 0.9% saline, (60 mL total)

Locations

Country	Name	City	State
United States	NC A&T State University	Greensboro	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	North Carolina Agriculture & Technical State University, North Carolina Translational and Clinical Sciences Institute

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Blood Butyrate Concentrations	Measure blood butyrate concentrations before, 30 minutes post, and 60 minutes post self-administration of the butyrate enemas	up to 1 hour post enema
Secondary	Interleukin-1 Beta (IL-1ß) Concentration	Blood biomarker samples were collected for the inflammatory cytokine IL-1ß.	up to 1 hour post enema