Effects of Alpha-1 Antagonist, Stress and Relaxation on Anorectal Functions
Condition: Constipation
MeSH terms: Constipation
Intervention: Alfuzosin; Placebo
Intervention description: oral alfuzosin immediate release (IR) 2.5 mg (Part A) or oral alfuzosin extended release (ER) 10 mg (Part B); placebo capsule identical to the study drug
Intervention MeSH terms: Alfuzosin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 74.0
Sex: Female
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study is designed to better understand the effects of effects of stress, relaxation, and
      a medication alfuzosin on bowel control and emptying in healthy people and patients with
      bowel problems.
    

Eligibility criteria:

        Inclusion criteria for controls (Part A only):

          -  Healthy

          -  Able to provide written informed consent before participating in the study

          -  Able to communicate adequately with the investigator and to comply with the
             requirements for the entire study.

        Inclusion criteria for patients (Parts A and B):

          -  Women with chronic constipation for 1 year with any 2 or more of the following
             symptoms for 3 months or longer, i.e. <3 bowel motions/week, straining ≥ 25% of time,
             hard or lumpy stools ≥ 25% of time, incomplete evacuation ≥ 25% of time, feeling of
             anorectal blockage ≥ 25% of time.

          -  Able to provide written informed consent before participating in the study

          -  Able to communicate adequately with the investigator and to comply with the
             requirements for the entire study.

        Exclusion criteria for controls (Part A); Items indicated with an asterisk (*) are also
        exclusion criteria for patients (Parts A and B):

          -  Clinical evidence of significant cardiovascular, respiratory, renal, hepatic,
             gastrointestinal, hematological, neurological, psychiatric or other disease that may
             interfere with the objectives of the study and/or pose safety concerns.*

          -  Current symptomatic orthostatic hypotension or history of hypotensive response as
             defined by a reduction of ≥ 30 mmHg in systolic or ≥ 20 mmHg in diastolic blood
             pressure.*

          -  Current symptoms of a functional gastrointestinal disorder assessed by questionnaire.

          -  Putative risk factors for pelvic floor trauma, i.e. six or more vaginal deliveries,
             birthweight >4500gms (macrosomia), or known 4th degree perineal tear.

          -  Inability to withdraw medications prior to the baseline period and throughout the
             study (except as protocol defined rescue medications):

               1. Medications that substantially alter GI transit* including laxatives, magnesium
                  and aluminum containing antacids, prokinetics, erythromycin, narcotics,
                  anti-cholinergics, tricyclic antidepressants, serotonin-norepinephrine reuptake
                  inhibitors (SNRI) and newer antidepressants

               2. Selective serotonin reuptake inhibitor (SSRI) antidepressants are permissible at
                  low, stable doses. All medications shall be reviewed and dis/approved by the
                  principal investigator on a case by case basis.*

               3. Potent Cytochrome P450 3A4 (Cyp3A4) inhibitors such as ketoconazole, itraconazole
                  and ritonavir, nitrates and phosphodiesterase inhibitors.* Note: stable doses of
                  thyroid replacement, estrogen replacement, low dose aspirin for cardioprotection,
                  and birth control (but with adequate backup contraception as drug-interactions
                  with birth control have not been conducted) are permissible.*

          -  Stable dose of thyroxine will be permitted*

          -  Prolonged Q-Tc interval > 500 msec on ECG within the last three months*

          -  Estimated glomerular filtration rate (eGFR) < 60 mL/minute. * Based on guidelines and
             recommendations from the National Kidney Disease Education Program (NKDEP) of the
             National Institutes of Health (NIH) and the Kidney Disease Outcomes Quality Initiative
             (KDOQI) of the National Kidney Foundation, the an eGFR using the Modification of Diet
             in Renal Disease (MDRD) Study equation is more accurate than a creatinine clearance
             calculated from serum and urine measurements. The formula is eGFR (mL/min/1.73 m2) =
             175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American).
             Based on our extensive experience in clinical practice and research studies, it is
             anticipated that all potentially eligible participants will have normal serum
             creatinine.

          -  History of allergies to alpha-1 adrenoreceptor antagonist*

          -  Active rectal inflammation, cancer; perianal sepsis; history of pelvic radiation,
             rectosigmoid surgery or inflammatory bowel disease*

          -  Pregnant women, prisoners and institutionalized individuals*

          -  Persons with a latex allergy.