Reduce Crohn's-Associated Diarrhea With Sodium Channel Therapy

Crohn's Disease Clinical Trial

— REACT  

Official title:

REACT Trial: A Randomized, Double Blind, Placebo-controlled, Crossover Study of Ranolazine for the Treatment of Crohn's Disease-associated Diarrhea

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04456517
• Other study ID #: 200640
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: October 18, 2022
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Crohn's disease is an inflammatory disorder that can affect any part of the gastrointestinal (GI) tract. Some patients still experience persistent diarrhea or other symptoms such as abdominal pain even when their Crohn's disease is in remission. Diarrhea and/or abdominal pain that is not responsive to standard therapies can significantly affect a patient's quality of life and ability to work. The purpose of this study is to test the safety and effectiveness of the drug ranolazine in reducing Crohn's disease-associated diarrhea and other symptoms. Ranolazine is approved by the US Food & Drug Administration (FDA) for chronic angina (a heart condition). This study is investigating if ranolazine could be used in the setting of Crohn's disease.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 16
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Meet diagnostic criteria for Crohn's Disease with active diarrhea Either with active disease or in remission (as defined by endoscopic or radiographic findings) but experiencing symptoms (e.g., diarrhea, abdominal pain)

• Have greater than three loose stools per day

Exclusion Criteria:

• Male and female subjects <18 years of age

• Significant change in medication including prednisone, antidepressant medications, or stimulants within the last 4 weeks

a. Allowances include: Rectal hydrocortisone, rectal mesalamine, addition of prednisone (up to 20mg) for flares, etc.

• Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use

• Severe psychiatric disease including schizophrenia, psychosis, suicidal depression

• Previous use of ranolazine within 2 months prior to enrollment

• Prior use of ranolazine which was discontinued for safety or tolerability

• Metabolic derangement defined as liver function tests >3x upper limit of normal or severe renal disease defined as calculated creatinine clearance <30 mL/min

• Have liver cirrhosis

• Concurrent use of CYP3A inhibitors, inducers, or substrates

a. These may include: ketoconazole, itraconazole, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir, clarithromycin, or rifampin, rifapentine, phenobarbital, phenytoin, and St. John's Wort, digoxin.

• A family history of (or congenital) long QT syndrome or known acquired QT interval prolongation

• Inability or refusal to give informed consent for any reason including a diagnosis of dementia or cognitive impairment

• Patients who are pregnant or breastfeeding

• Patients who are enrolled in other investigational drug studies or who have taken investigational drugs within 30 days before enrollment

• Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history) or prevent the participant from completing the protocol (poor compliance or unpredictable schedule)

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Diarrhea
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases

Intervention

Drug:
• Ranolazine
500 mg tablet
• Placebo
Ranolazine-matched placebo tablet

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in daily number of loose stools from baseline	Daily number of loose stools and antidiarrheal use will be collected directly from all subjects using MyCap or, if installation and use of an app is not possible, through email with a survey link. MyCap is a secure mobile application developed by the REDCap team at Vanderbilt and integrated into the REDCap database system.	Baseline to Week 36
Secondary	Mean change in Crohn's Disease Activity Index (CDAI) score	The Crohn's Disease Activity Index (CDAI) combines weighted scores of clinical and laboratory variables to estimate disease severity. The CDAI consists of eight variables, two of which are subjective, related to the disease, each weighted according to its ability to be predictive of disease activity. The absolute score ranges from 0 to 600. CDAI scores of less than 150 indicate a clinical remission and scores over 450 indicate severely active disease. Since blood draws will not be performed as part of this study, the hematocrit component of the CDAI will not be assessed.	Baseline to Week 36
Secondary	Mean change in Harvey Bradshaw Index (HBI) score	The Harvey-Bradshaw index (Harvey-Bradshaw Index - HBI) assesses the degree of illness (activity) in patients with Crohn's disease. The HBI consists of 5 items with a minimum score of 0 and a maximum attainable score depending on the number of stools the patient identifies per day. HBI scores < 5 are defined as clinical remission, HBI between 5 and 7 as mild disease, HBI between 8 and 16 as moderate disease, and HBI > 16 as severe disease.	Baseline to Week 36
Secondary	Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score	The SIBDQ is a 10-item questionnaire measuring quality of life in four domains: bowel symptoms, emotional health, systemic symptoms, and social function and is scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). The absolute score ranges are from 10 (poor Health-related quality of life) to 70 (optimum Health-related quality of life).	Baseline, Day 84, and Day 168
Secondary	Patient Health Questionnaire (PHQ-9) score	The PHQ-9 is a 9-item questionnaire that screens for the presence and severity of depression and can be used to make a depression diagnosis using DSM-IV criteria.; The PHQ-9 is scored on a 3-point Likert scale from 0 (not at all) to 3 (nearly every day). The absolute score ranges are from 0 (none or minimal depression) to 27 (severe depression).	Baseline, Day 84, Day 168