Crohn DiseaseIBDNCT05578313
Inflammatory Bowel Diseases (IBD) Cannabis Registry
An observational study of Crohn Disease and Ulcerative Colitis, run by Eli Sprecher, MD at 1 site in Israel.
Trial summary
The inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are characterized by lifelong relapsing-remitting gastrointestinal inflammation, with symptoms of abdominal pain, diarrhea, and rectal bleeding during active disease. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Crohn Disease, Ulcerative Colitis, Pouchitis
- What is being tested?
- Medical Cannabis
- How many people
- 1,000 participants
- Where
- 1 siteIsrael
- Study dates
- 10 Jul 2019to 10 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study population: Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating in the study, which have signed an informed consent form and answered to all the study inclusion criteria. Patients will be informed of the study by their treating physician, recruited and followed throughout the follow-up period by study co-ordinators. This study will include five patient groups:
Who may be able to join
- Patients (male and female, age 18-80 years) diagnosed with Crohn's disease (CD), ulcerative colitis (UC) or pouchitis, and healthy volunteers.
- All patients will sign an informed consent form. IBD patients who are recruited to group 3 will be included if they report mild-severe abdominal pain in clinical questioning of clinical activity (Harvey-Bradshaw index).
- Healthy participants recruited to group 2 will be healthy volunteers with no prior/current use of medical cannabis
Who cannot join
- Inability to sign an informed consent and complete the study protocol
- Unstable or uncontrolled medical disorder, or severe systemic disease (other than IBD)
- Participating in clinical interventional trial unrelated to cannabis derived preparations
- Ileostomy/ colostomy
- Pregnancy or intent to become pregnant in the next 6 month or breast feeding during the study
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center
Tel Aviv
Nitsan Maharshak, MD, 972527360384, nitsanm@tlvmc.gov.il
Naomi Fliss, PhD, 972524626445, naomifl@tlvmc.gov.il
About this study
The inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are characterized by lifelong relapsing-remitting gastrointestinal inflammation, with symptoms of abdominal pain, diarrhea, and rectal bleeding during active disease. Medical therapy reduces intestinal inflammation and ameliorates symptoms. Medical cannabis has recently been added to the arsenal of symptom-reducing measures in IBD. Though the efficacy of THC and CBD have been established as the two most dominant ingredients of cannabis, the rest of the plant phytochemicals are unknown, and effects on patients are not yet determined.
Read the detailed description
Hypothesis (es) and Aims:
Prospectively follow IBD patients receiving medical cannabis as treatment of their disease (group 1) in comparison to the following control groups:
- Healthy patients who do not use cannabis; 3) IBD patients who experience pain and do not use cannabis; 4) IBD patients who do not experience pain and do not use cannabis; 5) IBD patients previously prescribed cannabis and were identified to have positive effect on their disease
- Specific aims: a prospective trial to determine whether cannabis can induce remission in patients with IBD.
- To identify treatment regimens associated with treatment success in IBD patients.
- To identify treatment regimens associated with treatment side effects in IBD patients.
- To analyze the optimal drug level for disease management in various IBD patient types.
- Study design:
- A prospective cohort study
- Setting: prospectively collect clinical, behavioral, dietary and environmental data of IBD patients receiving medical cannabis as treatment of their disease. Data will be collected according to a uniform standardized protocol specifically adapted to the needs of the study.
- Study population:
Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating in the study, which have signed an informed consent form and answered to all the study inclusion criteria. Patients will be informed of the study by their treating physician, recruited and followed throughout the follow-up period by study coordinators.
This study will include five patient groups:
- Group 1 (study group): IBD patients prescribed cannabis as treatment for their bowel disease.
- Group 2 (Control group): One hundred healthy patients who do not use cannabis and are not eligible or not interested to commence this intervention.
- Group 3 (control group): Up to 100 IBD patient who experience pain and do not use cannabis
- Group 4 (control group): Up to 100 IBD patient who do not experience pain and do not use cannabis
- Group 5 (Cannabis responders group): up to 100 IBD patients previously prescribed cannabis and were identified to have positive effect on their disease *Study plan:
- Among the study group :
At baseline, demographic characteristics, medical history, concomitant medication assessment, disease related therapy and failed therapy will be documented.
Study visits:
Among the study group: recruitment at time 0, after one month (±14 days) of treatment, at three months (±21 days) and at 6 months (±30 days) of therapy (end of study), will be conducted, in which patients will be asked to fill in questionnaires, give biologic samples, undergo clinical, anthropometric and nutritional evaluation and physician assessment and monitoring of therapy, safety and adverse events. The cannabis producing company, composition, quantity and way of consumption will be documented.
•Among control group and Cannabis responders group: Healthy controls will be samples once at baseline. All IBD control groups (groups 3-5) will be followed up similarly as the study group and will undergo all sampling and questionnaires, at times 0, 3, 6 months (excluding the 1 month cannabis dose adjustment meeting).
Patients will be asked to inform in case of relapse during the follow up period and provide stool and blood samples before therapy is changed. At relapse time point, disease activity index will be recorded and questionnaires will be completed.
*Sample collection: Baseline and follow up study visits will include biologic samples collection (blood, feces) from which blood levels of complete blood count (CBC), Albumin, Liver enzymes (ALT, AST, ALP), lipid panel (Total cholesterol, LDL, HDL, triglycerides), creatinine, fasting glucose, C-reactive protein (CRP), drug levels and antibodies (for patients treated with thiopurines and biologics), and fecal levels of Calprotectin will be measured.
White blood cells will be separated and stored for m RNA analysis of cannabinoid metabolism. Only RNA fractions will be extracted and analyzed, no DNA will be assessed and no genetic sequencing will be performed . In addition, 10 ml of blood will be drawn for analysis of Th17 cells. CD4 T cells will be purified from peripheral blood of IBD patients by RosetteSep™ Human CD4+ T Cell Enrichment Cocktail kit. STAT3 and IL-17 levels will be analyzed. The samples analysis will be done at Dedi Meiri's lab at the Technion-IIT. Serum, and fecal samples will be stored at -80◦C for future analysis after being authorized by the IRB and by law including cannabis phytochemical analysis (10ml of each) on WBC and on biopsies when available and for fecal microbiome analysis. In appendix A- a detailed list of all tests in each visit.
*Endoscopic evaluation: In patients who will undergo a standard of care endoscopic examination for clinical reasons: these will include mucosal and histologic assessment for disease severity (SES-CD and MAYO score for CD and UC patients respectively, PDAI for Pouchitis patients).
Mucosal biopsies will be collected from inflamed and healthy areas, and from standard areas of the GI track (table 1), sent for histology assessment and stored for future analysis after being authorized by the IRB and by law. These samples will be stored in RNA Later snapped frozen and stored at -80◦c until analysis. No more than 10 samples will be collected during endoscopy including samples for clinical assessment. Samples from recto-sigmoid junction (20 cm from anus) will be taken in every colonoscopy, regardless of the status of inflammation.
*Biologic sample handling: Samples will be stored at -80◦c while coded with no identifying information; access to samples will be restricted to the study staff only. Samples will be stored up to 10 years from final data collection.
In this study, serum and fecal samples analyzed will include those gathered from protocol number 0276-19 and from protocol number 0250-17 in patients using medical cannabis only. In the later group, samples will be used only if the patient had agreed for use of samples in other studies other than 0250-17. To both studies, Professor Nitsan Maharshak is PI.
*Questionnaires:
Baseline and follow up study visits will include data collection from the following:
- Documentation of cannabis therapy: consumption method, quantity, THC/CBD concentration and cannabis strain/ barcode of preparation
- Food frequency questionnaire
- Food diary from last 3 days
- Lifestyle questionnaire
- Medical management questionnaire (IBD SES- self efficacy scale questionnaire)
- Patient reported outcomes (PROMIS) questionnaires
- Medical cannabis treatment evaluation questionnaire and Adverse events
- Big Five personality traits
Anthropometric and nutritional evaluation:
- Patients weight (kg), height (m), waist circumference (cm) will be documented at each study visit, and body mass index (BMI) will be calculated.
- Nutritional status will be evaluated by a MUST questionnaire *Study endpoints: the study will follow patients throughout 6 months of treatment and follow disease remission (clinical/biochemical) or exacerbation.
- Disease remission:
- Reduction in appropriate clinical scores
- Decrease in serum CRP or fecal CLP
- Endoscopic remission
- Disease exacerbation:
- Increase in appropriate clinical score
- Increase in fecal calprotectin levels (>250mg/gr OR 100 units higher than baseline levels)
- Emergency room visit due to disease symptoms, hospitalization, non-elective surgery.
- Diagnosis of active disease by endoscopy or imaging
- Medical treatment change by treating physician
- Statistical analysis:
Statistical analyses will be performed using SPSS version 23.0 for Windows. Patients who adhere to the study's protocol (defined as preforming ≥ 80% of exercises) will be included in data analysis. An intention-to-treat analysis will include patients excluded because of non-adherence to the intervention.
Descriptive statistics will be used to describe the distribution of variables associated with characteristics of the study sample. Continuous variables will be presented as means± SD and dichotomous/categorical variables as proportions. The normality of the distribution of continuous variables will be tested by the Kolmogorov-Smirnov test. If normality is rejected, non-parametric tests will be used.
Univariate analysis: To test the association between continuous variables with normal distribution, the Pearson correlation coefficient will be performed. To test associations between continuous variables which do not distribute normally or for ordinal variable, the spearman correlation coefficient will be used. To test differences in continuous variables between the treatments arms the t-test for independent groups (or Mann-Whitney test for non-normally distributed variables) will be performed. For comparison of dichotomous or categorical variables the Chi-square test will be performed.
To compare baseline to end of treatment parameters within arms for continuous variables the t-test for dependent groups will be performed (or Wilcoxson test for non-normally distributed variables), in dichotomous/categorical variables the McNemar Test will be performed.
To test differences in continuous variables between the treatment groups in numbers of time points the Mix model for repeated measures will be performed. To test differences in dichotomous/categorical variables between the treatment groups in numbers of time points Generalized estimating equation will be performed.
- Conditions
- Crohn Disease, Ulcerative Colitis, Pouchitis, Healthy
- Being tested
- Medical Cannabis
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative, Pouchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medical CannabisDrug
Patients will be observed throughout their treatment with medical cannabis, prescribed to them by for clinically treating their disease (treatment is not an intervention of the study).
| Study group | Role | What they receive |
|---|---|---|
| • Group 1 (study group) | IBD patients prescribed cannabis as treatment of their bowel disease. Receives: Drug: Medical Cannabis | |
| • Group 2 (Control group) | One hundred healthy patients who do not use cannabis and are not eligible or not interested to commence this intervention. | |
| • Group 3 (control group) | Up to 100 IBD patient who experience pain and do not use cannabis | |
| • Group 4 (control group) | Up to 100 IBD patient who do not experience pain and do not use cannabis | |
| • Group 5 (Cannabis responders group) | up to 100 IBD patients previously prescribed cannabis and were identified to have positive effect on their disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 4
Disease clinical response will be measured as the change in HBI scores from baseline to week 4.
A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7.
Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Measured: week 4
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 4
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 4.
A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis
SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
Measured: week 4
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 12
Disease clinical response will be measured as the change in HBI scores from baseline to week 12.
A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7.
Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Measured: week 12
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 12
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 12.
A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis
SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
Measured: week 12
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 24
Disease clinical response will be measured as the change in HBI scores from baseline to week 24.
A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7.
Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Measured: Week 24
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 24
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 24.
A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis
SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
Measured: Week 24
Secondary outcomes (18)
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 4
Disease remission will be defined by HBI <5
Higher HBI clinical score means higher disease severity:
Remission<5 Mild Disease 5-7 Moderate Disease 8-16 Severe Disease >16
Measured: week 4
Determine clinical remission rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 4
Disease remission will be defined by SCCAI <3
SCCAI (Simple Clinical Colitis Activity Index) score range from 0 to 19. Higher score means higher disease severity.
Measured: week 4
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 12
Disease remission will be defined by HBI <5
Higher HBI clinical score means higher disease severity:
Remission<5 Mild Disease 5-7 Moderate Disease 8-16 Severe Disease >16
Measured: week 12
Determine clinical remission rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 12
Disease remission will be defined by SCCAI <3
SCCAI (Simple Clinical Colitis Activity Index) score range from 0 to 19. Higher score means higher disease severity.
Measured: week 12
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 24
Disease remission will be defined by HBI <5
Higher HBI clinical score means higher disease severity:
Remission<5 Mild Disease 5-7 Moderate Disease 8-16 Severe Disease >16
Measured: week 24
Determine clinical remission rates SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 24
Disease remission will be defined by SCCAI <3
SCCAI (Simple Clinical Colitis Activity Index) score range from 0 to 19. Higher score means higher disease severity.
Measured: week 24
Determine endoscopic response rates using Simple Endoscopic Score for Crohn Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 4
Endoscopic response will be defined as decrease of ≥50% in SES-CD score from baseline to week 4
Higher SES-CD score means higher disease activity and severity. A drop > 50% is considered an endoscopic response
Measured: week 4
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 4
Endoscopic response will be defined as reduction in Endoscopic Mayo score ≤ 1 for Ulcerative Colitis
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 4
Determine endoscopic response rates using Simple Endoscopic Score for Crohn Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 12
Endoscopic response will be defined as decrease of ≥50% in SES-CD score from baseline to week 12
Higher SES-CD score means higher disease activity and severity. A drop > 50% is considered an endoscopic response
Measured: week 12
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 12
Endoscopic response will be defined as reduction in Endoscopic Mayo score ≤ 1 for from baseline to week 12
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 12
Determine endoscopic response rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 24
Endoscopic response will be defined as decrease of ≥50% in SES-CD score from baseline to week 24
Higher SES-CD score means higher disease activity and severity. A drop > 50% is considered an endoscopic response
Measured: week 24
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 24
Endoscopic response will be defined as reduction in Endoscopic Mayo score ≤ 1 for from baseline to week 24
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 24
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 4
Endoscopic remission will be defined as SES-CD<4 for Crohn's disease
SES-CD ranges from a minimum score o and has no high limit. Higher SES-CD score means higher disease severity and activity.
Measured: week 4
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 4
Endoscopic remission will be defined as Endoscopic Mayo score = 0 for ulcerative colitis
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 4
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 12
Endoscopic remission will be defined as SES-CD<4 for Crohn's disease
SES-CD ranges from a minimum score o and has no high limit. Higher SES-CD score means higher disease severity and activity.
Measured: week 12
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 12
Endoscopic remission will be defined as Endoscopic Mayo score = 0 for ulcerative colitis
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 12
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 24
Endoscopic remission will be defined as SES-CD<4 for Crohn's disease
SES-CD ranges from a minimum score o and has no high limit. Higher SES-CD score means higher disease severity and activity.
Measured: week 24
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 24
Endoscopic remission will be defined as Endoscopic Mayo score = 0 for Ulcerative Colitis
Endoscopic Mayo score range from 0-3. Higher score means higher disease severity
Measured: week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start10 Jul 2019
- Primary completion10 Jul 2023 (estimated)
- Study completion10 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Sprecher, MD
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Eli Sprecher, MD, Tel-Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05578313
- Sponsor's protocol ID
- TLV_0276-19
- Acronym
- IBD
- Status last verified
- Oct 2022
- First submitted
- 30 Jun 2021
- Last updated
- 13 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory Bowel Diseases (IBD) Cannabis Registry
- ClinicalTrials.gov ID
- NCT05578313
- Acronym / sponsor ID
- IBD / TLV_0276-19
- Conditions
- Crohn Disease, Ulcerative Colitis, Pouchitis, Healthy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Eli Sprecher, MDOther government
- Study start
- 10 Jul 2019 (actual)
- Primary completion
- 10 Jul 2023 (estimated)
- Study completion
- 10 Jul 2024 (estimated)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are characterized by lifelong relapsing-remitting gastrointestinal inflammation, with symptoms of abdominal pain, diarrhea, and rectal bleeding during active disease. Medical therapy reduces intestinal inflammation and ameliorates symptoms. Medical cannabis has recently been added to the arsenal of symptom-reducing measures in IBD. Though the efficacy of THC and CBD have been established as the two most dominant ingredients of cannabis, the rest of the plant phytochemicals are unknown, and effects on patients are not yet determined.
Detailed description
Hypothesis (es) and Aims:
Prospectively follow IBD patients receiving medical cannabis as treatment of their disease (group 1) in comparison to the following control groups:
- Healthy patients who do not use cannabis; 3) IBD patients who experience pain and do not use cannabis; 4) IBD patients who do not experience pain and do not use cannabis; 5) IBD patients previously prescribed cannabis and were identified to have positive effect on their disease
- Specific aims: a prospective trial to determine whether cannabis can induce remission in patients with IBD.
- To identify treatment regimens associated with treatment success in IBD patients.
- To identify treatment regimens associated with treatment side effects in IBD patients.
- To analyze the optimal drug level for disease management in various IBD patient types.
- Study design:
- A prospective cohort study
- Setting: prospectively collect clinical, behavioral, dietary and environmental data of IBD patients receiving medical cannabis as treatment of their disease. Data will be collected according to a uniform standardized protocol specifically adapted to the needs of the study.
- Study population:
Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating in the study, which have signed an informed consent form and answered to all the study inclusion criteria. Patients will be informed of the study by their treating physician, recruited and followed throughout the follow-up period by study coordinators.
This study will include five patient groups:
- Group 1 (study group): IBD patients prescribed cannabis as treatment for their bowel disease.
- Group 2 (Control group): One hundred healthy patients who do not use cannabis and are not eligible or not interested to commence this intervention.
- Group 3 (control group): Up to 100 IBD patient who experience pain and do not use cannabis
- Group 4 (control group): Up to 100 IBD patient who do not experience pain and do not use cannabis
- Group 5 (Cannabis responders group): up to 100 IBD patients previously prescribed cannabis and were identified to have positive effect on their disease *Study plan:
- Among the study group :
At baseline, demographic characteristics, medical history, concomitant medication assessment, disease related therapy and failed therapy will be documented.
Study visits:
Among the study group: recruitment at time 0, after one month (±14 days) of treatment, at three months (±21 days) and at 6 months (±30 days) of therapy (end of study), will be conducted, in which patients will be asked to fill in questionnaires, give biologic samples, undergo clinical, anthropometric and nutritional evaluation and physician assessment and monitoring of therapy, safety and adverse events. The cannabis producing company, composition, quantity and way of consumption will be documented.
•Among control group and Cannabis responders group: Healthy controls will be samples once at baseline. All IBD control groups (groups 3-5) will be followed up similarly as the study group and will undergo all sampling and questionnaires, at times 0, 3, 6 months (excluding the 1 month cannabis dose adjustment meeting).
Patients will be asked to inform in case of relapse during the follow up period and provide stool and blood samples before therapy is changed. At relapse time point, disease activity index will be recorded and questionnaires will be completed.
*Sample collection: Baseline and follow up study visits will include biologic samples collection (blood, feces) from which blood levels of complete blood count (CBC), Albumin, Liver enzymes (ALT, AST, ALP), lipid panel (Total cholesterol, LDL, HDL, triglycerides), creatinine, fasting glucose, C-reactive protein (CRP), drug levels and antibodies (for patients treated with thiopurines and biologics), and fecal levels of Calprotectin will be measured.
White blood cells will be separated and stored for m RNA analysis of cannabinoid metabolism. Only RNA fractions will be extracted and analyzed, no DNA will be assessed and no genetic sequencing will be performed . In addition, 10 ml of blood will be drawn for analysis of Th17 cells. CD4 T cells will be purified from peripheral blood of IBD patients by RosetteSep™ Human CD4+ T Cell Enrichment Cocktail kit. STAT3 and IL-17 levels will be analyzed. The samples analysis will be done at Dedi Meiri's lab at the Technion-IIT. Serum, and fecal samples will be stored at -80◦C for future analysis after being authorized by the IRB and by law including cannabis phytochemical analysis (10ml of each) on WBC and on biopsies when available and for fecal microbiome analysis. In appendix A- a detailed list of all tests in each visit.
*Endoscopic evaluation: In patients who will undergo a standard of care endoscopic examination for clinical reasons: these will include mucosal and histologic assessment for disease severity (SES-CD and MAYO score for CD and UC patients respectively, PDAI for Pouchitis patients).
Mucosal biopsies will be collected from inflamed and healthy areas, and from standard areas of the GI track (table 1), sent for histology assessment and stored for future analysis after being authorized by the IRB and by law. These samples will be stored in RNA Later snapped frozen and stored at -80◦c until analysis. No more than 10 samples will be collected during endoscopy including samples for clinical assessment. Samples from recto-sigmoid junction (20 cm from anus) will be taken in every colonoscopy, regardless of the status of inflammation.
*Biologic sample handling: Samples will be stored at -80◦c while coded with no identifying information; access to samples will be restricted to the study staff only. Samples will be stored up to 10 years from final data collection.
In this study, serum and fecal samples analyzed will include those gathered from protocol number 0276-19 and from protocol number 0250-17 in patients using medical cannabis only. In the later group, samples will be used only if the patient had agreed for use of samples in other studies other than 0250-17. To both studies, Professor Nitsan Maharshak is PI.
*Questionnaires:
Baseline and follow up study visits will include data collection from the following:
- Documentation of cannabis therapy: consumption method, quantity, THC/CBD concentration and cannabis strain/ barcode of preparation
- Food frequency questionnaire
- Food diary from last 3 days
- Lifestyle questionnaire
- Medical management questionnaire (IBD SES- self efficacy scale questionnaire)
- Patient reported outcomes (PROMIS) questionnaires
- Medical cannabis treatment evaluation questionnaire and Adverse events
- Big Five personality traits
Anthropometric and nutritional evaluation:
- Patients weight (kg), height (m), waist circumference (cm) will be documented at each study visit, and body mass index (BMI) will be calculated.
- Nutritional status will be evaluated by a MUST questionnaire *Study endpoints: the study will follow patients throughout 6 months of treatment and follow disease remission (clinical/biochemical) or exacerbation.
- Disease remission:
- Reduction in appropriate clinical scores
- Decrease in serum CRP or fecal CLP
- Endoscopic remission
- Disease exacerbation:
- Increase in appropriate clinical score
- Increase in fecal calprotectin levels (>250mg/gr OR 100 units higher than baseline levels)
- Emergency room visit due to disease symptoms, hospitalization, non-elective surgery.
- Diagnosis of active disease by endoscopy or imaging
- Medical treatment change by treating physician
- Statistical analysis:
Statistical analyses will be performed using SPSS version 23.0 for Windows. Patients who adhere to the study's protocol (defined as preforming ≥ 80% of exercises) will be included in data analysis. An intention-to-treat analysis will include patients excluded because of non-adherence to the intervention.
Descriptive statistics will be used to describe the distribution of variables associated with characteristics of the study sample. Continuous variables will be presented as means± SD and dichotomous/categorical variables as proportions. The normality of the distribution of continuous variables will be tested by the Kolmogorov-Smirnov test. If normality is rejected, non-parametric tests will be used.
Univariate analysis: To test the association between continuous variables with normal distribution, the Pearson correlation coefficient will be performed. To test associations between continuous variables which do not distribute normally or for ordinal variable, the spearman correlation coefficient will be used. To test differences in continuous variables between the treatments arms the t-test for independent groups (or Mann-Whitney test for non-normally distributed variables) will be performed. For comparison of dichotomous or categorical variables the Chi-square test will be performed.
To compare baseline to end of treatment parameters within arms for continuous variables the t-test for dependent groups will be performed (or Wilcoxson test for non-normally distributed variables), in dichotomous/categorical variables the McNemar Test will be performed.
To test differences in continuous variables between the treatment groups in numbers of time points the Mix model for repeated measures will be performed. To test differences in dichotomous/categorical variables between the treatment groups in numbers of time points Generalized estimating equation will be performed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| • Group 1 (study group) | – | Drug: Medical CannabisIBD patients prescribed cannabis as treatment of their bowel disease. |
| • Group 2 (Control group) | – | –One hundred healthy patients who do not use cannabis and are not eligible or not interested to commence this intervention. |
| • Group 3 (control group) | – | –Up to 100 IBD patient who experience pain and do not use cannabis |
| • Group 4 (control group) | – | –Up to 100 IBD patient who do not experience pain and do not use cannabis |
| • Group 5 (Cannabis responders group) | – | –up to 100 IBD patients previously prescribed cannabis and were identified to have positive effect on their disease |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study population: Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating in the study, which have signed an informed consent form and answered to all the study inclusion criteria. Patients will be informed of the study by their treating physician, recruited and followed throughout the follow-up period by study co-ordinators. This study will include five patient groups:
Key inclusion criteria (3 listed)
- Patients (male and female, age 18-80 years) diagnosed with Crohn's disease (CD), ulcerative colitis (UC) or pouchitis, and healthy volunteers.
- All patients will sign an informed consent form. IBD patients who are recruited to group 3 will be included if they report mild-severe abdominal pain in clinical questioning of clinical activity (Harvey-Bradshaw index).
- Healthy participants recruited to group 2 will be healthy volunteers with no prior/current use of medical cannabis
Key exclusion criteria (5 listed)
- Inability to sign an informed consent and complete the study protocol
- Unstable or uncontrolled medical disorder, or severe systemic disease (other than IBD)
- Participating in clinical interventional trial unrelated to cannabis derived preparations
- Ileostomy/ colostomy
- Pregnancy or intent to become pregnant in the next 6 month or breast feeding during the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Medical CannabisPatients will be observed throughout their treatment with medical cannabis, prescribed to them by for clinically treating their disease (treatment is not an intervention of the study). | Drug | • Group 1 (study group) |
Primary outcome
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 4
Time frame: week 4
Disease clinical response will be measured as the change in HBI scores from baseline to week 4. A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7. Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 4
Time frame: week 4
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 4. A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 12
Time frame: week 12
Disease clinical response will be measured as the change in HBI scores from baseline to week 12. A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7. Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 12
Time frame: week 12
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 12. A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 24
Time frame: Week 24
Disease clinical response will be measured as the change in HBI scores from baseline to week 24. A clinical response is defined as reduction of at least 3 points in HBI score, ∆HBI>3 in patients with baseline HBI>7. Harvey-Bradshaw Index (HBI) is a tool for assessing the degree of illness (activity) in patient's with Crohn's disease. Higher score means higher disease activity and severity. A drop > 3 is considered a clinical response.
Determine the clinical response rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 24
Time frame: Week 24
Disease clinical response will be measured as the change in SCCAI scores from baseline to week 24. A clinical response is defined as reduction of at list 30% in SCCAI score, ∆SCCAI>30% for Ulcerative Colitis SCCAI (Simple Clinical Colitis Activity Index) is used to assess the severity of symptoms in people who suffer from ulcerative colitis. Score range from 0 to 19 points 0<SCCAI<19. Higher score means higher disease activity and severity.
18 secondary outcomes
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 4
Time frame: week 4
Determine clinical remission rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 4
Time frame: week 4
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 12
Time frame: week 12
Determine clinical remission rates using SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 12
Time frame: week 12
Determine clinical remission rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at weeks 24
Time frame: week 24
Determine clinical remission rates SCCAI (Simple Clinical Colitis Activity Index) in patients with Ulcerative Colitis receiving cannabis at week 24
Time frame: week 24
Determine endoscopic response rates using Simple Endoscopic Score for Crohn Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 4
Time frame: week 4
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 4
Time frame: week 4
Determine endoscopic response rates using Simple Endoscopic Score for Crohn Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 12
Time frame: week 12
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 12
Time frame: week 12
Determine endoscopic response rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at weeks 24
Time frame: week 24
Determine endoscopic response rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 24
Time frame: week 24
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 4
Time frame: week 4
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 4
Time frame: week 4
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 12
Time frame: week 12
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 12
Time frame: week 12
Determine endoscopic remission rates using Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease receiving cannabis at week 24
Time frame: week 24
Determine endoscopic remission rates using Mayo score in patients with Ulcerative Colitis receiving cannabis at weeks 24
Time frame: week 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Crohn Disease and Ulcerative Colitis, run by Eli Sprecher, MD at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nitsanm Maharshak, Professor (+972527360384, nitsanm@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine patients clinical response rates using Harvey-Bradshaw Index (HBI) in Crohn's disease patients receiving cannabis at week 4 (time frame: week 4). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2022.