Effects of Alpha-1 Antagonist, Stress and Relaxation on Anorectal Functions

NCT ID: NCT01834729

Last Updated: 2019-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2017-09-06

Brief 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.

Detailed Description

Normally, bowel emptying requires relaxation of the anal sphincter (i.e., lowermost end of intestinal tract) and pelvic muscles. Some people cannot relax these muscles normally and experience constipation. Alfuzosin is a medication which is approved to treat bladder but not bowel problems.

Conditions

Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alfuzosin

In Part A, subjects randomized to this arm will receive a single dose of oral alfuzosin immediate release (IR) 2.5 mg.

In Part B, only constipated patients will receive oral alfuzosin (10 mg extended release (ER)) capsules.

Group Type: EXPERIMENTAL

Alfuzosin

Intervention Type: DRUG

oral alfuzosin immediate release (IR) 2.5 mg (Part A) or oral alfuzosin extended release (ER) 10 mg (Part B)

Placebo

Subjects randomized to this arm will receive a single placebo capsule identical to the study drug.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

placebo capsule identical to the study drug

Interventions

Alfuzosin

oral alfuzosin immediate release (IR) 2.5 mg (Part A) or oral alfuzosin extended release (ER) 10 mg (Part B)

Intervention Type: DRUG

Placebo

placebo capsule identical to the study drug

Intervention Type: OTHER

Other Intervention Names

Xatral (immediate release 2.5 mg); Uroxatral (extended release 10 mg)

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Adil Bharucha

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adil Bharucha, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Rochester

Rochester, Minnesota, United States

Countries

United States

References

Chakraborty S, Feuerhak K, Muthyala A, Harmsen WS, Bailey KR, Bharucha AE. Effects of Alfuzosin, an alpha1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders. Clin Gastroenterol Hepatol. 2019 May;17(6):1138-1147.e3. doi: 10.1016/j.cgh.2018.08.036. Epub 2018 Aug 18.

Reference Type: RESULT

PMID: 30130627 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01DK078924

Identifier Type: NIH

Identifier Source: secondary_id

View Link

12-006090

Identifier Type: -

Identifier Source: org_study_id