<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04415333</url>
  </required_header>
  <id_info>
    <org_study_id>18-1680</org_study_id>
    <nct_id>NCT04415333</nct_id>
  </id_info>
  <brief_title>Gut Butyrate and Blood Pressure in African Americans</brief_title>
  <official_title>Effect of Gut Butyrate Delivery on Blood Pressure in African Americans With Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>North Carolina Translational and Clinical Sciences Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>North Carolina Agriculture &amp; Technical State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      African Americans have the greatest burden of hypertension. Recently, the short-chain fatty&#xD;
      acid, butyrate, has been reported to have some effect on blood pressure. Butyrate is not&#xD;
      normally ingested since it is made by bacteria in the gut as a byproduct of fiber&#xD;
      fermentation. In this proof of concept study, the investigators will investigate the effect&#xD;
      of butyrate absorbed in the gut (via the participant self-administering an enema with&#xD;
      butyrate) has on blood pressure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Description: African Americans (AA) have the greatest burden of hypertension. Recently, gut&#xD;
      microbial dysbiosis (a term that describes a poorly diverse gut microbial profile and lower&#xD;
      short-chain fatty acid (SCFA) production) has been linked to hypertension and may be involved&#xD;
      in the pathogenesis of hypertension in African Americans. African Americans have been&#xD;
      reported to have lower gut SCFA and SCFA can reduce blood pressure. This is a proof of&#xD;
      concept pilot study to determine the relationship between gut SCFA and blood pressure (BP).&#xD;
      Delivery of butyrate to the gut will be via enema.&#xD;
&#xD;
      Objectives: The objectives of this research are to 1. Identify gut microbial taxa (SCFA&#xD;
      butyrate-producing microbes) and circulating butyrate levels associated with hypertension via&#xD;
      a cross-sectional design in AA without and with hypertension. 2. Quantify the relationship&#xD;
      between SCFA (butyrate) absorption into the bloodstream and subsequent changes in blood&#xD;
      pressure in a 24-hour period after delivering butyrate into the gut via enema.&#xD;
&#xD;
      Participants: African Americans males and females ages of 30-50 without hypertension (normal&#xD;
      BP/healthy control; systolic BP: 90-129/ diastolic BP: 60-89mmHg) and with hypertension&#xD;
      (systolic BP: 130-159 mmHg/ diastolic BP: 80-99 mmHg) that do not take anti-hypertension&#xD;
      medication will be recruited.&#xD;
&#xD;
      Description of Study: There are 2 groups; control (without hypertension; BP:&#xD;
      90-129/60-89mmHg; 5 male/5 female, n=10) and experimental (with hypertension; BP&#xD;
      130-159/80-99 mmHg; 5 male/5 female, n=10). Normotensive participants (control group) will be&#xD;
      age (±1 year) and sex-matched to hypertensive group participants. All participants (control&#xD;
      and experimental groups; 5 male/5 female) will provide stool and blood samples, and complete&#xD;
      24-hour (hr) ambulatory blood pressure (ABP) monitoring to compare the abundance of fecal&#xD;
      butyrate-producing microbes, circulating (blood) butyrate concentrations, and average blood&#xD;
      pressure responses during the day and overnight. Individuals in the control group will only&#xD;
      participate in donating stool (1-time) and a blood sample (1-time) and wearing a 24-hr ABP&#xD;
      monitor (1-day). In a crossover blinded randomized controlled pilot study, the 10&#xD;
      hypertensive AA subjects (5 male/5 female) will be randomized to self-administer a sodium&#xD;
      butyrate (80mmol butyrate in 0.9% saline, 60 ml total) or control (low dose) butyrate (5mmol&#xD;
      butyrate 0.9%, 60 ml total) enema 1 week apart (7 days). Subjects will provide a stool sample&#xD;
      before each study day (2 total), have their BP measured via ABP monitor, submit to a blood&#xD;
      draws (pre-enema-baseline), self-administer the randomized enema, submit to a 30 min &amp; 60 min&#xD;
      post-enema blood draw, and wear the 24-hour ABP monitor for the remainder of that day.&#xD;
      Subjects will be provided with written and verbal instructions on how to self-administer the&#xD;
      enema. The dietary supplement (sodium butyrate) will be compounded by a local pharmacy&#xD;
      (Custom Care Pharmacy - 109 Pisgah Church Rd. Greensboro, NC) into an enema at the&#xD;
      concentrations listed above.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2021</start_date>
  <completion_date type="Actual">November 2, 2021</completion_date>
  <primary_completion_date type="Actual">November 1, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Daytime Blood Pressure</measure>
    <time_frame>approximately 16 hours post enema</time_frame>
    <description>Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Nighttime Blood Pressure</measure>
    <time_frame>approximately 8 hours post enema</time_frame>
    <description>Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood Butyrate Concentrations</measure>
    <time_frame>up to 1 hour post enema</time_frame>
    <description>Measure blood butyrate concentrations before, 30 minutes post, and 60 minutes post self-administration of the butyrate enemas</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Butyrate 5 mmol</intervention_name>
    <description>Enema-based delivery of 5 mmol butyrate in 0.9% saline, (60 mL total)</description>
    <arm_group_label>Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]</arm_group_label>
    <arm_group_label>Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Butyrate 80 mmol</intervention_name>
    <description>Enema-based delivery of 80 mmol butyrate in 0.9% saline, (60 mL total)</description>
    <arm_group_label>Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]</arm_group_label>
    <arm_group_label>Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Normotensive (control subjects without hypertension): In order to be eligible to&#xD;
        participate in this study, an individual must meet all of the following criteria (which&#xD;
        will be assessed after an initial telephone interview and at Visit 1 (screening and consent&#xD;
        visit):&#xD;
&#xD;
          -  Provision of signed and dated informed consent form&#xD;
&#xD;
          -  Be an African American adult (man or woman) between 30 - 50 years of age with normal&#xD;
             blood pressure (never diagnosed with hypertension) (systolic: 90-129 and diastolic:&#xD;
             60-89 mmHg).&#xD;
&#xD;
          -  Body Mass Index of 18.5-30 kg/m^2&#xD;
&#xD;
          -  Not have any other diagnosed cardiovascular disease&#xD;
&#xD;
          -  Not exercise regularly (Participate in less than 60 minutes of exercise/week)&#xD;
&#xD;
          -  Not be pregnant or be lactating&#xD;
&#xD;
          -  Be free of active diseases that affect your intestines (i.e., chronic constipation,&#xD;
             diarrhea, Crohn's disease, ulcerative colitis, irritable bowel syndrome,&#xD;
             diverticulosis, stomach or duodenal ulcers, diabetes, hepatitis, HIV, and cancer)&#xD;
&#xD;
          -  Have not taken antibiotics in the past 3 months&#xD;
&#xD;
          -  Have not been regularly taking medications that impact intestinal function (i.e.,&#xD;
             laxatives, enemas, anti-diarrheal agents, narcotics, antacids, antispasmodics,&#xD;
             antidepressants, anticonvulsants, antibiotics, herbals, homeopathy, and home remedies)&#xD;
             or fiber supplements.&#xD;
&#xD;
          -  Have no plans of travel out of town during the study periods.&#xD;
&#xD;
          -  Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study&#xD;
             duration&#xD;
&#xD;
        Hypertension subjects not on anti-hypertension medication (intervention group). The pool of&#xD;
        subjects that do not take hypertension medication may be limited. If a heavily medicated&#xD;
        subject population is encountered, the investigators may include subjects taking diuretics&#xD;
        only: In order to be eligible to participate in this study, an individual must meet all of&#xD;
        the following criteria (which will be assessed after an initial telephone interview and at&#xD;
        Visit 1 (screening and consent visit):&#xD;
&#xD;
          -  Provision of signed and dated informed consent form. Letter of clearance or signature&#xD;
             of PCP on informed consent.&#xD;
&#xD;
          -  Be an African American adult (man or woman) between 30 - 50 years of age with stage-1&#xD;
             to stage-2 hypertension (systolic: 130-159 and diastolic: 80-99 mmHg).&#xD;
&#xD;
          -  Not taking any anti-hypertension medications (although the investigators may enroll&#xD;
             individuals only taking a diuretic where resting BP levels are within the range of&#xD;
             stage-1 hypertension: systolic BP 130-140 mmHg. Subjects can resume taking the&#xD;
             diuretic after they remove the monitor).&#xD;
&#xD;
          -  Body Mass Index of 18.5-30 kg/m^2&#xD;
&#xD;
          -  Not have any other diagnosed cardiovascular disease&#xD;
&#xD;
          -  Not exercise regularly (Participate in less than 60 minutes of exercise/week)&#xD;
&#xD;
          -  Not be pregnant or be lactating&#xD;
&#xD;
          -  Be free of active diseases that affect your intestines (i.e., chronic constipation,&#xD;
             diarrhea, Crohn's disease, ulcerative colitis, irritable bowel syndrome,&#xD;
             diverticulosis, stomach or duodenal ulcers, diabetes, hepatitis, HIV, and cancer)&#xD;
&#xD;
          -  Have not taken antibiotics in the past 3 months&#xD;
&#xD;
          -  Have not been regularly taking medications that impact intestinal function (i.e.,&#xD;
             laxatives, enemas, anti-diarrheal agents, narcotics, antacids, antispasmodics,&#xD;
             antidepressants, diuretics, anticonvulsants, antibiotics, herbals, homeopathy, and&#xD;
             home remedies) or fiber supplements.&#xD;
&#xD;
          -  Have no plans of travel out of town during the study periods.&#xD;
&#xD;
          -  Agreement to adhere to Lifestyle Considerations throughout study duration&#xD;
&#xD;
        Exclusion Criteria for both groups:&#xD;
&#xD;
          -  Exercise more than 60 minutes per week for more than 4 consecutive weeks.&#xD;
&#xD;
          -  Diagnosed with stroke, history of myocardial infarction (heart attack); liver, lung,&#xD;
             or kidney diseases; peripheral vascular disease or cancer within the last 6 months.&#xD;
&#xD;
          -  Presence of metabolic disease (diabetes mellitus), inflammatory diseases (e.g.,&#xD;
             inflammatory bowel diseases, rheumatoid arthritis, and systemic lupus erythematosus);&#xD;
             kidney stones or gallbladder problems; diagnosed liver, lung or kidney diseases;&#xD;
&#xD;
          -  Pregnancy, lactation, or actively trying to conceive.&#xD;
&#xD;
          -  Taking anti-hypertension medications (i.e., calcium channel blockers, ACE inhibitors,&#xD;
             angiotensin- receptor blockers, β-blockers, vasodilators, etc.) other than diuretics&#xD;
             (e.g., hydrochlorothiazide, chlorothiazide, furosemide, etc) or medications known to&#xD;
             affect inflammation or metabolic function (anti-inflammatories, statins, thyroid&#xD;
             medication) in the past 1 month. If diuretics are used, subjects may able to&#xD;
             participate if they agree to refrain from taking their diuretic the day of the&#xD;
             experiment. In this instance, resting systolic BP while on their medication will still&#xD;
             need to be greater than 130 mmHg.&#xD;
&#xD;
          -  Current smoker or tobacco use within the last 10 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc D Cook, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>North Carolina A&amp;T State Univeristy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NC A&amp;T State University</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>8899080</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19460106</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>20471725</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>24343275</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>February 18, 2022</last_update_submitted>
  <last_update_submitted_qc>February 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>African American</keyword>
  <keyword>Blood pressure</keyword>
  <keyword>Gut Microbiome</keyword>
  <keyword>Short-chain fatty acid</keyword>
  <keyword>Butyrate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Butyric Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The investigators will share the informed consent and de-identified data set including fecal microbiome sequencing, blood pressure data, circulating butyrate levels in an online repository (Carolina Digital Repository).</ipd_description>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>3-5 years after the completion of the primary endpoint.</ipd_time_frame>
    <ipd_access_criteria>Contact Dr. Marc Cook (mdcook@ncat.edu) at NC A&amp;T State University. The data set will be shared in the Carolina Digital repository.</ipd_access_criteria>
    <ipd_url>https://library.unc.edu/scholarly-communications/open-access/carolina-digital-repository-cdr/</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>De-identified data set</doc_type>
      <doc_url>https://library.unc.edu/scholarly-communications/open-access/carolina-digital-repository-cdr/</doc_url>
      <doc_comment>Data will be accessible at the above Carolina Data Repository for the UNC library system.</doc_comment>
    </study_doc>
  </study_docs>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT04415333/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>August 15, 2022</submitted>
    <submission_canceled>December 13, 2022</submission_canceled>
    <submitted>December 13, 2022</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04415333
org study id: 18-1680
nct id: NCT04415333
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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: 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.
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.
primary purpose: Other
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.
measure: Mean Daytime Blood Pressure
time frame: approximately 16 hours post enema
description: Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.
measure: Mean Nighttime Blood Pressure
time frame: approximately 8 hours post enema
description: Immediately following self-administration of butyrate enema, participants will be fitted with an ambulatory blood pressure monitor to be worn for 24 hours.
measure: Blood Butyrate Concentrations
time frame: up to 1 hour post enema
description: Measure blood butyrate concentrations before, 30 minutes post, and 60 minutes post self-administration of the butyrate enemas
arm group label: Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]
arm group type: Experimental
description: 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).
arm group label: Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]
arm group type: Experimental
description: 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).
arm group label: Control
arm group type: No Intervention
description: 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.
intervention type: Drug
intervention name: Sodium Butyrate 5 mmol
description: Enema-based delivery of 5 mmol butyrate in 0.9% saline, (60 mL total)
arm group label: Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]
arm group label: Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]
intervention type: Drug
intervention name: Sodium Butyrate 80 mmol
description: Enema-based delivery of 80 mmol butyrate in 0.9% saline, (60 mL total)
arm group label: Sodium Butyrate [5 mmol] first, then Sodium Butyrate [80 mmol]
arm group label: Sodium Butyrate [80 mmol] first, then Sodium Butyrate [5 mmol]
criteria: 
gender: All
minimum age: 30 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marc D Cook, PhD
role: Principal Investigator
affiliation: North Carolina A&T State Univeristy
facility: 
country: United States
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.
PMID: 8899080
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.
PMID: 19460106
citation: 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
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.
PMID: 24343275
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Butyric Acid
sharing ipd: Yes
ipd description: The investigators will share the informed consent and de-identified data set including fecal microbiome sequencing, blood pressure data, circulating butyrate levels in an online repository (Carolina Digital Repository).
ipd info type: Informed Consent Form (ICF)
ipd time frame: 3-5 years after the completion of the primary endpoint.
ipd 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.
ipd url: https://library.unc.edu/scholarly-communications/open-access/carolina-digital-repository-cdr/
study doc: 
provided document: 
submitted: August 15, 2022
submission canceled: December 13, 2022
submitted: December 13, 2022