Gut Butyrate and Blood Pressure in African Americans
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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.
    

Intervention name(s): Sodium Butyrate 5 mmol; Sodium Butyrate 80 mmol
Intervention type(s): Drug; Drug
Intervention description(s): Enema-based delivery of 5 mmol butyrate in 0.9% saline, (60 mL total); Enema-based delivery of 80 mmol butyrate in 0.9% saline, (60 mL total)
Intervention MeSH terms: Butyric Acid
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: African American; Blood pressure; Gut Microbiome; Short-chain fatty acid; Butyrate