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

NCT01834729 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 12-0060901UL1RR024150R01DK078924
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Constipation

Outcome Measures

Primary Outcomes (2)

• Weekly Rate of Spontaneous Bowel Movements at 4 Weeks

  A bowel movement is considered a spontaneous bowel movement (SBM) if no laxative, enema, or suppository was taken in the preceding 24 hours.

  4 weeks

• Weekly Rate of Complete Spontaneous Bowel Movements at 4 Weeks

  If the subject indicates that the spontaneous bowel movement (SBM) was associated with a sensation of complete bowel emptying, the SBM will be counted as a complete spontaneous bowel movement (CSBM).

  4 weeks

Study Arms (2)

Alfuzosin

EXPERIMENTAL

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.

Drug: Alfuzosin

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Alfuzosin DRUG

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

Also known as: Xatral (immediate release 2.5 mg), Uroxatral (extended release 10 mg)

Alfuzosin

Placebo OTHER

placebo capsule identical to the study drug

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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):
• 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
• 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.\*
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Center for Research Resources (NCRR): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 30130627 RESULT

MeSH Terms

Conditions

Constipation

Interventions

alfuzosin

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Men were not studied; baseline bowel diary was not preceded by a run-in period; treatment phase only lasted 2 weeks.

Results Point of Contact

• Title: Dr. Adil E. Bharucha
• Organization: Mayo Clinic

bharucha.adil@mayo.edu

507-284-2687

Study Officials

• Adil Bharucha, MBBS, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 18, 2013
• Study Start: March 1, 2013
• Primary Completion: September 6, 2017
• Study Completion: September 6, 2017
• Last Updated: January 29, 2019
• Results First Posted: January 11, 2019

Record last verified: 2019-01

Locations

US (1)