Clinical trial NCT04456517: Reduce Crohn's-Associated Diarrhea With Sodium Channel Therapy
Official title: REACT Trial: A Randomized, Double Blind, Placebo-controlled, Crossover Study of Ranolazine for the Treatment of Crohn's Disease-associated Diarrhea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Inflammatory Bowel Disease
Keywords: Diarrhea
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2020-07-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants receive one of two alternative interventions during the initial phase of the study and receive the other intervention during the second phase of the study
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Daily Number of Loose Stools
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Crohn's Disease Activity Index (CDAI) Score
timeFrame: Baseline to 12 weeks
measure: Harvey Bradshaw Index (HBI) Score
timeFrame: Baseline to Week 12
measure: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score
timeFrame: Baseline to 12 weeks
measure: Patient Health Questionnaire (PHQ-9) Score
timeFrame: Baseline to week 12
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Dawn B. Beaulieu, MD
role: PRINCIPAL_INVESTIGATOR
References: