Gut Butyrate and Blood Pressure in African Americans
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Sodium Butyrate 5 mmol; Sodium Butyrate 80 mmol
Intervention description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
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)
Masking description: 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.
Enrollment: 20.0
Sex: All
Minimum age: 30 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: African American; Blood pressure; Gut Microbiome; Short-chain fatty acid; Butyrate

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.
    

Eligibility criteria:

        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, 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