Crohn's Disease, Inflammatory Bowel Disease
Conditions
Keywords
Diarrhea
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.
Interventions
DRUGRanolazine
500 mg tablet
DRUGPlacebo
Ranolazine-matched placebo tablet
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Number of Loose Stools | Baseline to 12 weeks | Daily number of loose stools will be collected directly from all subjects using MyCap. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Crohn's Disease Activity Index (CDAI) Score | Baseline to 12 weeks | 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. |
| Harvey Bradshaw Index (HBI) Score | Baseline to Week 12 | 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. |
| Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | Baseline to 12 weeks | 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). |
| Patient Health Questionnaire (PHQ-9) Score | Baseline to week 12 | 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). |
Countries
United States
Participant flow
Pre-assignment details
4 of 4 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine, Then Placebo \- Participants first receive a Ranolazine 500 mg tablet twice daily for 12 weeks, they then receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms
Ranolazine: 500 mg tablet
Placebo: Ranolazine-matched placebo tablet | 3 |
| Placebo, Then Ranolazine \- Participants first receive a Placebo tablet (matching Ranolazine 500 mg tablets) twice daily for 12 weeks, they then receive a Ranolazine 500mg tablet twice daily for 12 weeks. This treatment will be given to participants with either active CD or patients with CD that is in remission but who experience continued symptoms
Ranolazine: 500 mg tablet
Placebo: Ranolazine-matched placebo tablet | 1 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention:Baseline to 12 Weeks | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo, Then Ranolazine | Total | Ranolazine, Then Placebo |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 9.1 | 43 years STANDARD_DEVIATION 13.2 | 37.7 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 1 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 0 / 3 | 1 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Daily Number of Loose Stools
Daily number of loose stools will be collected directly from all subjects using MyCap.
Time frame: Baseline to 12 weeks
Population: 1 subject in Placebo arm only has baseline data since they withdrew.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Daily Number of Loose Stools | Liquid Stools at Baseline | 3.6 number of liquid stools | Standard Deviation 2.5 |
| Ranolazine | Daily Number of Loose Stools | Liquid stools at Week 12 | 2.9 number of liquid stools | Standard Deviation 1.6 |
| Placebo | Daily Number of Loose Stools | Liquid Stools at Baseline | 4.5 number of liquid stools | Standard Deviation 3.4 |
| Placebo | Daily Number of Loose Stools | Liquid stools at Week 12 | 3.2 number of liquid stools | Standard Deviation 0.8 |
Secondary
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.
Time frame: Baseline to 12 weeks
Population: One of three subjects on ranolazine did not have a baseline CDAI score. 1 of 4 subject on placebo did not complete course.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Crohn's Disease Activity Index (CDAI) Score | Baseline CDAI | 169 score on a scale | Standard Deviation 90.5 |
| Ranolazine | Crohn's Disease Activity Index (CDAI) Score | 12 week CDAI | 100 score on a scale | Standard Deviation 99.6 |
| Placebo | Crohn's Disease Activity Index (CDAI) Score | Baseline CDAI | 117 score on a scale | Standard Deviation 88.1 |
| Placebo | Crohn's Disease Activity Index (CDAI) Score | 12 week CDAI | 110.3 score on a scale | Standard Deviation 97.8 |
Secondary
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.
Time frame: Baseline to Week 12
Population: 1 of 4 subjects assigned placebo for 12 weeks did not complete course.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Harvey Bradshaw Index (HBI) Score | Baseline HBI | 6.7 score on a scale | Standard Deviation 1.5 |
| Ranolazine | Harvey Bradshaw Index (HBI) Score | 12 week HBI | 4.7 score on a scale | Standard Deviation 3.5 |
| Placebo | Harvey Bradshaw Index (HBI) Score | Baseline HBI | 5 score on a scale | Standard Deviation 3.1 |
| Placebo | Harvey Bradshaw Index (HBI) Score | 12 week HBI | 5 score on a scale | Standard Deviation 1.7 |
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).
Time frame: Baseline to week 12
Population: 1 of 4 subjects in placebo arm did not complete course.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Patient Health Questionnaire (PHQ-9) Score | Baseline PHQ9 | 8.3 score on a scale | Standard Deviation 5.5 |
| Ranolazine | Patient Health Questionnaire (PHQ-9) Score | 12 week PHQ9 | 5.7 score on a scale | Standard Deviation 3.5 |
| Placebo | Patient Health Questionnaire (PHQ-9) Score | Baseline PHQ9 | 7 score on a scale | Standard Deviation 3.9 |
| Placebo | Patient Health Questionnaire (PHQ-9) Score | 12 week PHQ9 | 6.3 score on a scale | Standard Deviation 3.8 |
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).
Time frame: Baseline to 12 weeks
Population: 1 of 4 subjects in placebo arm did not complete course.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | Baseline SIBDQ | 52 score on a scale | Standard Deviation 10.5 |
| Ranolazine | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | Week 12 SIBDQ | 57.3 score on a scale | Standard Deviation 8.1 |
| Placebo | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | Baseline SIBDQ | 54 score on a scale | Standard Deviation 10.1 |
| Placebo | Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Score | Week 12 SIBDQ | 59.3 score on a scale | Standard Deviation 5.9 |