Ulcerative ColitisPhase 1/2NCT03720002
HF2 Therapy in the Treatment of Active Ulcerative Colitis
A Phase 1/2 study testing HF2 in people with Ulcerative Colitis, run by Sheba Medical Center at 2 sites in 2 countries.
Trial summary
This is a phase I-II study with the herbal formulation (HF2) for treatment of active ulcerative colitis This will be a two-stage study: Stage 1 will comprise an open label single arm exploratory study of 10 active ulcerative colitis (UC) patients investigating oral HF2 therapy for induction of remission in outpatients… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- HF2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 29 May 2019to 1 Feb 2023
- Phase
- Phase 1/2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Established diagnosis of UC
- Age- 18-70
- active UC defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a score of ≥2 in the modified Mayo endoscopic sub-score.
- Stable medication dose or if the patient has discontinued previous treatment :
- for Infliximab or Vedolizumab - at least one month after patient received last dose; for Adalimumab, Golimumab, immunomodulator, corticosteroids, 5ASA - at least two weeks after patient received last dose.
Who cannot join
- non-controlled renal or liver disease, hypertension, cardiovascular disease, cerebrovascular disease, chronic pancreatitis, diabetes mellitus, gallstone disease, uncontrolled migraines or neurological disorders
- significant laboratory abnormalities, including anemia with hemoglobin <10, leucopenia , thrombocytopenia , abnormal coagulation tests , or elevation of liver or kidney function tests above the normal values.
- active infection, sepsis or pneumonia.
- pregnancy/nursing
- known allergy to the compound
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: HF2 Therapy in the Treatment of Active Ulcerative Colitis:
This is a phase I-II study with the herbal formulation (HF2) for treatment of active ulcerative colitis
This will be a two-stage study:
Read more
Stage 1 will comprise an open label single arm exploratory study of 10 active ulcerative colitis (UC) patients investigating oral HF2 therapy for induction of remission in outpatients with active UC. Active disease is defined as (SCCAI) score ≥5 and a score of ≥2 in the modified Mayo endoscopic sub-score. Clinical remission is defined as a SCCAI score of ≤2 The patients will receive HF2 therapy for 4 weeks. Stage 2: If clinical response (defined as a drop of ≥3 points of the SCCAI score ) is achieved in ≥ 3 patients and no significant safety signals will emerge, the investigators will proceed to a prospective pilot randomized placebo-controlled study. Patients will be randomized into one of two arms: HF2 once daily or placebo formulation (2:1 proportion) for 8 weeks.
The primary outcome for stage 2 is a co-primary outcome of clinical response (reduction in SCCAI of ≤3 OR achievement of clinical remission defined as SCCAI ≤2) coupled with an objective evidence of response (Mayo score improvement of ≥1 or 50% FcAL reduction) at week 8.
Patients clinically responding at week 8, will be eligible to continue in an 8-weeks extension study to receive either placebo or 1.5gr/day curcumin alone until week 16, as per their original allocation. Exploratory analysis of outcomes for the extension study will include the percentage of patients in clinical remission (SCCAI≤2) and the percentage of patients who maintained clinical response (reduction in SCCAI of ≥3 point compared to week 0).
Read the detailed description
1.1 Objective: To investigate the efficacy and safety of HF2 to induce remission in patients with active UC.
1.2 Methods:
This will be a two-stage study:
Stage 1 will comprise an open label single arm exploratory study of 10 active UC patients investigating HF2 therapy for induction of remission in outpatients with active UC.
Stage 2: If clinical response is achieved in ≥ 3 patients and no significant safety signals will emerge, the investigators will proceed to a prospective pilot randomized placebo-controlled study.
Stage 1: Open label study
1.7 Primary outcome stage I The primary outcome will be the percentage of patients in clinical remission (SCCAI score of ≤2) at week 4 after initiation of therapy
Secondary outcomes (phase 1):
1.7.1 The percentage of patients who had a rapid clinical response at day 7 after induction of therapy 1.7.2 The percentage of patients who had a clinical response at week 4 after initiation of therapy 1.7.3 Improvement in endoscopic score at week 4 compared to baseline according to modified endoscopic Mayo score (improvement of ≥ 1 point) 1.7.4 Achievement of mucosal healing (endoscopic modified Mayo score of ≤1). 1.7.5 Percentage of patients who achieve normalization and/or >50% improvement in C-reactive protein (CRP) and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices).
1.7.6 Time-to-response defined as number of days to achieve a drop of ≥3 points of the SCCAI score.
1.7.7. Time-to-ceasing of bleeding, defined as number of days for complete absence of blood in stools (SCCAI bleeding sub-score of 0), in those patients who has at least some blood in stool at entry (SCCAI bleeding sub-score of 1 or more).
1.7.8 The percentage of patients in clinical remission at day 7 after induction of therapy.
1.7.9. Improvement in IBD quality of life as gauged by questionnaire (IBDQ). 2 Intervention: Patients diagnosed with active UC will receive HF2 therapy for 4 weeks. 3 Procedures: 3.2 At inclusion: clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography 3.4 clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography
Stage II: A multicenter randomized placebo controlled trial. The study will be performed in Sheba Medical Center and up to 2 additional European centers (TBD). For this stage of the trial , the patients will received HF2 combintation or similar (as described above) (2:1 allocation) for 8 weeks. After completion of 8 weeks, all responders previously on active drug will receive additional 8 weeks of oral curcumin or placebo as per original arm.
Primary outcome: a composite outcome of clinical response (reduction in SCCAI of ≤3 OR achievement of clinical remiision defined as SCCAI ≤2) coupled with an objective evidence of response ( Mayo score improvement of ≥1 or 50% FcAL reduction ) at week 8
Secondary outcomes:
- Percentage of patients in clinical remission (SCCAI≤2) at week 8
- The percentage of patients who had a clinical response at week 8 after initiation of therapy
- Improvement in endoscopic score at week 8 compared to baseline according to endoscopic Mayo score (improvement of ≥ 1 point)
- Achievement of mucosal healing (endoscopic modified Mayo score of ≤1) at week 8
- Percentage of patients who achieve normalization and/or >50% improvement of CRP and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices) at week 8.
- Percentage of patients in corticosteroid-free clinical remission at week 8
- Improvement in IBD quality of life as gauged by questionnaire (IBDQ).
- Percentage of patients in clinical remission at week 16
- Percentage of patients with clinical response at week 16
- Percentage of patients with normalized fecal calprotectin and CRP
6.2. Intervention: Patients will be randomized into one of two arms: HF2 or placebo formulation (2:1 proportion) for 8 weeks. Following the first 8 weeks, responders w ill receive an additional 8 weeks of curcumin 1.5 g/d or placebo (as per original arm).
Patients will undergo clinical, laboratory (CRP, biomarkers, blood chemistry, CBC_biomarker (CRP and fecal calprotectin, at week 0,4,8 and 16 , and endoscopic assessment at baseline and week 8. Cardiac echo and liver US will be performed at week 0 and 8.
Corticosteroid tapering will be allowed as per treating physician's discretion after week 8.
- Conditions
- Ulcerative Colitis
- Being tested
- HF2
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HF2Dietary supplement
placebo
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Experimental | Will receive HF2 add-on Receives: Dietary Supplement: HF2 |
| Placebo | Placebo comparator | Will receive placebo Receives: Dietary Supplement: HF2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage I: Clinical remission
achievement of remission in the symptoms of the disease (defined as Simple Clinical Colitis Activity Index -SCCAI score of ≤2)
Measured: week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start29 May 2019
- Primary completion1 Feb 2023
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After an initial open-label run-in (if successful) the patients will be randomized to receive HF2 or placebo (2:1 allocation)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720002
- Sponsor's protocol ID
- SHEBA-17-4232-UK-CTIL
- Status last verified
- Nov 2021
- First submitted
- 21 Oct 2018
- Last updated
- 14 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ben-Horin S, Salomon N, Karampekos G, Viazis N, Lahat A, Ungar B, Eliakim R, Kuperstein R, Kriger-Sharabi O, Reiss-Mintz H, Yanai H, Dotan I, Zittan E, Maharshak N, Hirsch A, Weitman M, Mantzaris GJ, Kopylov U. Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2024 Feb;22(2):347-356.e6. doi: 10.1016/j.cgh.2023.05.023. Epub 2023 Jun 9.
PubMed 37302449
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HF2 Therapy in the Treatment of Active Ulcerative Colitis:
- ClinicalTrials.gov ID
- NCT03720002
- Acronym / sponsor ID
- SHEBA-17-4232-UK-CTIL
- Conditions
- Ulcerative Colitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 29 May 2019 (actual)
- Primary completion
- 1 Feb 2023 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 25 Oct 2018 (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.
This is a phase I-II study with the herbal formulation (HF2) for treatment of active ulcerative colitis
This will be a two-stage study:
Stage 1 will comprise an open label single arm exploratory study of 10 active ulcerative colitis (UC) patients investigating oral HF2 therapy for induction of remission in outpatients with active UC. Active disease is defined as (SCCAI) score ≥5 and a score of ≥2 in the modified Mayo endoscopic sub-score. Clinical remission is defined as a SCCAI score of ≤2 The patients will receive HF2 therapy for 4 weeks. Stage 2: If clinical response (defined as a drop of ≥3 points of the SCCAI score ) is achieved in ≥ 3 patients and no significant safety signals will emerge, the investigators will proceed to a prospective pilot randomized placebo-controlled study. Patients will be randomized into one of two arms: HF2 once daily or placebo formulation (2:1 proportion) for 8 weeks.
The primary outcome for stage 2 is a co-primary outcome of clinical response (reduction in SCCAI of ≤3 OR achievement of clinical remission defined as SCCAI ≤2) coupled with an objective evidence of response (Mayo score improvement of ≥1 or 50% FcAL reduction) at week 8.
Patients clinically responding at week 8, will be eligible to continue in an 8-weeks extension study to receive either placebo or 1.5gr/day curcumin alone until week 16, as per their original allocation. Exploratory analysis of outcomes for the extension study will include the percentage of patients in clinical remission (SCCAI≤2) and the percentage of patients who maintained clinical response (reduction in SCCAI of ≥3 point compared to week 0).
Detailed description
1.1 Objective: To investigate the efficacy and safety of HF2 to induce remission in patients with active UC.
1.2 Methods:
This will be a two-stage study:
Stage 1 will comprise an open label single arm exploratory study of 10 active UC patients investigating HF2 therapy for induction of remission in outpatients with active UC.
Stage 2: If clinical response is achieved in ≥ 3 patients and no significant safety signals will emerge, the investigators will proceed to a prospective pilot randomized placebo-controlled study.
Stage 1: Open label study
1.7 Primary outcome stage I The primary outcome will be the percentage of patients in clinical remission (SCCAI score of ≤2) at week 4 after initiation of therapy
Secondary outcomes (phase 1):
1.7.1 The percentage of patients who had a rapid clinical response at day 7 after induction of therapy 1.7.2 The percentage of patients who had a clinical response at week 4 after initiation of therapy 1.7.3 Improvement in endoscopic score at week 4 compared to baseline according to modified endoscopic Mayo score (improvement of ≥ 1 point) 1.7.4 Achievement of mucosal healing (endoscopic modified Mayo score of ≤1). 1.7.5 Percentage of patients who achieve normalization and/or >50% improvement in C-reactive protein (CRP) and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices).
1.7.6 Time-to-response defined as number of days to achieve a drop of ≥3 points of the SCCAI score.
1.7.7. Time-to-ceasing of bleeding, defined as number of days for complete absence of blood in stools (SCCAI bleeding sub-score of 0), in those patients who has at least some blood in stool at entry (SCCAI bleeding sub-score of 1 or more).
1.7.8 The percentage of patients in clinical remission at day 7 after induction of therapy.
1.7.9. Improvement in IBD quality of life as gauged by questionnaire (IBDQ). 2 Intervention: Patients diagnosed with active UC will receive HF2 therapy for 4 weeks. 3 Procedures: 3.2 At inclusion: clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography 3.4 clinical and endoscopic assessment, blood and stool tests, cardiac echo and liver ultrasonography
Stage II: A multicenter randomized placebo controlled trial. The study will be performed in Sheba Medical Center and up to 2 additional European centers (TBD). For this stage of the trial , the patients will received HF2 combintation or similar (as described above) (2:1 allocation) for 8 weeks. After completion of 8 weeks, all responders previously on active drug will receive additional 8 weeks of oral curcumin or placebo as per original arm.
Primary outcome: a composite outcome of clinical response (reduction in SCCAI of ≤3 OR achievement of clinical remiision defined as SCCAI ≤2) coupled with an objective evidence of response ( Mayo score improvement of ≥1 or 50% FcAL reduction ) at week 8
Secondary outcomes:
- Percentage of patients in clinical remission (SCCAI≤2) at week 8
- The percentage of patients who had a clinical response at week 8 after initiation of therapy
- Improvement in endoscopic score at week 8 compared to baseline according to endoscopic Mayo score (improvement of ≥ 1 point)
- Achievement of mucosal healing (endoscopic modified Mayo score of ≤1) at week 8
- Percentage of patients who achieve normalization and/or >50% improvement of CRP and/or calprotectin levels (computed out of patients with abnormal values at baseline for these indices) at week 8.
- Percentage of patients in corticosteroid-free clinical remission at week 8
- Improvement in IBD quality of life as gauged by questionnaire (IBDQ).
- Percentage of patients in clinical remission at week 16
- Percentage of patients with clinical response at week 16
- Percentage of patients with normalized fecal calprotectin and CRP
6.2. Intervention: Patients will be randomized into one of two arms: HF2 or placebo formulation (2:1 proportion) for 8 weeks. Following the first 8 weeks, responders w ill receive an additional 8 weeks of curcumin 1.5 g/d or placebo (as per original arm).
Patients will undergo clinical, laboratory (CRP, biomarkers, blood chemistry, CBC_biomarker (CRP and fecal calprotectin, at week 0,4,8 and 16 , and endoscopic assessment at baseline and week 8. Cardiac echo and liver US will be performed at week 0 and 8.
Corticosteroid tapering will be allowed as per treating physician's discretion after week 8.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- After an initial open-label run-in (if successful) the patients will be randomized to receive HF2 or placebo (2:1 allocation)
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Experimental | Dietary Supplement: HF2Will receive HF2 add-on |
| Placebo | Placebo comparator | Dietary Supplement: HF2Will receive placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Established diagnosis of UC
- Age- 18-70
- active UC defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a score of ≥2 in the modified Mayo endoscopic sub-score.
- Stable medication dose or if the patient has discontinued previous treatment :
- for Infliximab or Vedolizumab - at least one month after patient received last dose; for Adalimumab, Golimumab, immunomodulator, corticosteroids, 5ASA - at least two weeks after patient received last dose.
Key exclusion criteria (5 listed)
- non-controlled renal or liver disease, hypertension, cardiovascular disease, cerebrovascular disease, chronic pancreatitis, diabetes mellitus, gallstone disease, uncontrolled migraines or neurological disorders
- significant laboratory abnormalities, including anemia with hemoglobin <10, leucopenia , thrombocytopenia , abnormal coagulation tests , or elevation of liver or kidney function tests above the normal values.
- active infection, sepsis or pneumonia.
- pregnancy/nursing
- known allergy to the compound
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 |
|---|---|---|
| HF2placebo | Dietary supplement | Active treatment, Placebo |
Primary outcome
Stage I: Clinical remission
Time frame: week 4
achievement of remission in the symptoms of the disease (defined as Simple Clinical Colitis Activity Index -SCCAI score of ≤2)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Derived from this study: PubMed 37302449Ben-Horin S, Salomon N, Karampekos G, Viazis N, Lahat A, Ungar B, Eliakim R, Kuperstein R, Kriger-Sharabi O, Reiss-Mintz H, Yanai H, Dotan I, Zittan E, Maharshak N, Hirsch A, Weitman M, Mantzaris GJ, Kopylov U. Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2024 Feb;22(2):347-356.e6. doi: 10.1016/j.cgh.2023.05.023. Epub 2023 Jun 9.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HF2 in people with Ulcerative Colitis, run by Sheba Medical Center at 2 sites in 2 countries.
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 5 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: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece, 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage I: Clinical remission (time frame: week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03720002, which also lists 1 linked publication.
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 14 Apr 2023.