Propionyl-L-Carnitine Hydrochloride in Patients With Mild Ulcerative Colitis; Efficacy, Safety and Tolerability Study

November 4, 2016 updated by: sigma-tau i.f.r. S.p.A.

Phase III Randomized Multicenter International Study to Investigate the Safety and Efficacy of Propionyl-L-Carnitine Hydrochloride Modified Release Tablets in Patients Affected by Mild Ulcerative Colitis Under Oral Stable Treatment

The aim of the trial is to test safety, tolerability and efficacy of Propionyl-L-carnitine modified release tablets 1g/die in reducing the symptoms of the disease with respect to the proportion of patients with disease remission at the end of the 8 weeks of treatment. It will also aim to investigate capability of the treatment in the maintenance of remission after four weeks of treatment interruption; histological changes will be also evaluated and finally, improvement in the overall quality of life as measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) will be investigated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Although it seems clear that an abnormal function of the colonic epithelium is the central problem causing inflammation and the unusual immunological response to the normal gut flora in inflammatory bowel disease (IBD), the actual causes of these dysfunctions are still unknown. Short Chain Fatty Acids (SCFA) are the main fuel of the colonic epithelium, and are normally produced by the bacterial flora by fermentation of the complex carbohydrates forming non soluble fibers usually introduced with everyday diet. Butyrate alone contributes 70% of the normal colonocyte energy. Studies done using animal models and colonic mucosa biopsies from patients suffering form ulcerative colitis (UC) have consistently shown that a metabolic change occurs in diseased colonic mucosa, with an impairment of butyrate oxidation (and of beta-oxidation) and an energy shortage that is only incompletely compensated by oxidation of glucose and other substrates such as glutamine. It is also well known that matrix metalloproteases production is highly increased in IBD and that serum transglutaminase activity is significantly reduced in patients with IBD. Transglutaminases are enzymes contributing to the crosslinking of matrix proteins and the reduction seen in patients affected by IBD correlates well with the endoscopic and histopathologic grading in UC, meaning that part of the circulating enzyme is sequestered in the injured colonic tissue in the effort to re-build the extracellular matrix during the healing process. Propionyl-L-carnitine Hydrochloride (PLC) is a molecule that has already been shown to reduce membrane lipid peroxidation in endothelial cells from bovine aorta and coronary vessels, to reduce the effects of hypoxia in coronary endothelial cells, and to play a role in the cardiac metabolic abnormalities that contribute to the mechanical dysfunctions leading to heart failure. Given these properties of Propionyl-L-carnitine Hydrochloride (ST 261) and given the peroxidative damage suffered by colonocytes in UC together with their metabolic impairment, the use of this molecule for the treatment of UC seemed to be appropriate and sound, in particular as a carrier of a propionate moiety that, once transformed into succinate, enters the Kreb cycle, acting as an extra burst fuel improving the balance of energy production inside tissues. Previous clinical experience has shown that PLC promoted complete or nearly complete regression of cutaneous trophic ulcers in a large number of vasculopathic patients refractory to all other therapies. As far as the UC pathology is concerned, the effects of ST 261, given orally or intrarectally, were investigated at different dosages, in preclinical experimentation, either after a single trinitrobenzene sulphonic acid (TNBS) administration (acute colitis) or after repeated TNBS administrations (reactivated colitis). The results showed a reduction in the damaged colon area both in acute model and reactivated colitis, even if the beneficial effect of restoration of TNBS-induced alterations of tissue morphology is more evident in the reactivated colitis model, particularly after oral administration. Based on the above-described results a development plan in humans started to investigate the activity of PLC in the treatment of ulcerative colitis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Landeskrankenhaus-Universitätskliniken Innsbruck - Klinische Abteilung für Gastroenterologie und Hepatologie
      • Salzburg, Austria, 5010
        • Krankenhaus der Barmherzigen Brüder - Abteilung für Innere Medizin
      • Vienna, Austria, 1190
        • Ordinationszentrum Döbling
      • Wien, Austria, 1090
        • Allgemeines Krankenhaus Wien - Universitätsklinik Klinik für Innere Medizin III
  • France
      • Creteil, France, 94010
        • Centre Hospitalier Intercommunal Créteil 40 avenue de Verdun
      • Marseille, France, 13015
        • Centre Hospitalier Universitaire Hôpital Nord - Service D'Hépato-Gastro-Entérologie
      • Nantes, France, 44000
        • Centre Hospitalier Universitaire Hotel Dieu Service d'hépato-gastroentérologie
      • Nice cedex 3, France, 06202
        • Hôpital de I´Archet 2 Service d'Hépato-Gastroentérologie et de Nutrition Clinicque, Pôle Digestif
      • Picardie, France, 80 054
        • Hôpital Nord - Dept. of Gastroenterology
      • Reims cedex, France, 51092
        • Hôpital Robert Debré Service et Consultation d'Hépato-Gastro-Entérologie
      • Saint-Etienne, France, 42270
        • Hopital Nord - CHU de Saint-Etienne Service de Gastro-Entérologie
      • Toulouse Cedex 4, France, 31079
        • Hôpital Rangueil Service de gastro-enterologie
      • Vandoeuvre Les Nancy Cedex, France, 54511
        • Hôpital Brabois Service de gastro-enterologie
  • Germany
      • Berlin, Germany, 10117
        • Charité Universitätsmedizin Berlin Universitätsklinik Charité, Campus Mitte Medizinische Poliklinik
      • Bochum, Germany, 44791
        • Saint Josef Hospital Ruhr Universitaet Bochum Gudrunstraße 56
      • Braunschweig, Germany, 38126
        • Klinikum Braunschweig
      • Dresden, Germany, 01307
        • Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I
      • Lübeck, Germany, 23538
        • Universtätsklinikum Schleswig-Holstein Gastroenterologie
      • Magdeburg, Germany, 39120
        • Universitätsklinikum Magdeburg A.ö.R. Klinik für Gastroenterologie, Hepatologie und Infektiologie
      • Mannheim, Germany, 68167
        • Universitätsmedizin Mannheim II. Medizinische Klinik
      • München, Germany, 80639
        • Praxis Prof. Dr. med. Herbert Kellner
      • Münster, Germany, 48149
        • Universitätklinikum Münster Medizinische Klinik und Poliklinik für Innere Medizin
      • Münster, Germany, 48159
        • Gastroenterologische Fachpraxis Am Germania Campus
      • Stade, Germany, 21682
        • Elbe Klinikum Stade Innere Medizin, Abteilung Gastroenterology
  • Hungary
      • Budapest, Hungary, 1136
        • Pannonia Maganorvosi Centrum Kft.
      • Budapest, Hungary, 1076
        • Fovárosi Önkormányzat Péterfy Sándor Utcai Kórház
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem 1st Internal Dept.
      • Budapest, Hungary, H-1088
        • Semmelweis Egyetem II. Sz. Belgyógyászati Klinika
      • Gyula, Hungary, 5700
        • Békés Megyei Képviselotestület Pándy Kálmán Kórháza Semmelweis ulica 1
      • Kaposvár, Hungary, H-7400
        • Kaposi Mór Megyei Oktató Kórhaz Belgyógyászati Osztály
      • Miskolc, Hungary, 3526
        • Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház II. sz. Belgyógyászati Osztály
      • Mosonmagyaróvar, Hungary, 9200
        • Karolina Kórház Rendelointézet Belgyógyászat- Gasztroenterológiai Osztály
      • Szekszárd, Hungary, 7100
        • Clinfan Kft. SMO
      • Szikszó, Hungary, 3800
        • CRU Hungary Kft.
  • Latvia
      • Daugavpils, Latvia, LV-5400
        • Daugavpils Central Regional Hospital
      • Riga, Latvia, LV-1002
        • Paula Stradina Clinical University Hospital Gastroenterology Centre
      • Riga, Latvia, LV-1005
        • Latvian Maritime Medicine Centre
      • Riga, Latvia, LV-1006
        • Digestive Disease Center GASTRO
  • Lithuania
      • Kaunas, Lithuania, LT-50009
        • Lietuvos sveikatos mokslu universiteto ligonine VšI Kauno klinikos Gastroenterologijos skyrius
      • Klaipeda, Lithuania, LT-92288
        • Klaipedos jurininku ligonine Diagnostikos skyrius
      • Vilnius, Lithuania, LT-03215
        • VšI Mykolo Marcinkeviciaus ligonines
      • Vilnius, Lithuania, LT-08661
        • Vilniaus universiteto ligonine Santariškiu klinikos Hepatologijos, gastroenterologijos ir dietologijos centras
  • Poland
      • Ksawerów, Poland, 95-054
        • Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp.J
      • Lódz, Poland, 90-153
        • SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego Oddzial Gastroenterologii Ogólnej i Onkologicznej
      • Olsztyn, Poland, 10-561
        • Wojewódzki Szpital Specjalistyczny w Olsztynie Oddzial Gastroenterologii
      • Sopot, Poland, 81-756
        • Endoskopia Sp. z o.o.
      • Warszawa, Poland, 03-580
        • NZOZ Vivamed
      • Wroclaw, Poland, 53-025
        • LexMedica
      • Wroclaw, Poland, 50-556
        • Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu Klinika Gastroenterologii i Hepatologii
      • Wroclaw, Poland, 51-149
        • Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego we Wroclawiu Oddzial Gastroenterologii
      • Wroclaw, Poland, 53-333
        • ARS MEDICA s.c., Rybak Maria, Rybak Zbigniew
  • Spain
      • Alcorcón, Spain, 28922
        • Fundación Hospital de Alcorcón Servicio de Gastroenterología
      • Barcelona, Spain, 08022
        • Centro Medico Teknon Servicio de Aparato Disgestivo
      • El Palmar, Spain, 30120
        • Hospital Universitario Virgen de la Arrixaca Servicio de Digestivo
      • Madrid, Spain, 28006
        • Hospital Universitario La Princesa Unidad de Hepatología, Servicio de Gastroenterologia
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz Servico de Gastroenterologia
      • Sabadell, Spain, 08028
        • Corporació Sanitaria Parc Taulí Servicio de Digestivo
      • Santander, Spain, 39008
        • Hospital Universitario Marques de Valdecilla Servicio de Digestivo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have read the Information for the Patient and signed the Informed Consent Form.
  • Diagnosis of active ulcerative colitis since at least 4 weeks as confirmed endoscopically and histologically.
  • Disease Activity Index comprised between 3 and 6, inclusive (mild ulcerative colitis), with rectal bleeding sub-score of at least 1.
  • Stable background oral aminosalicylates (mesalazine, balsalazide, olsalazine) or sulfasalazine standard therapy for greater than or equal to 4 weeks prior to screening assessments.
  • If female, not pregnant or nursing. For women of childbearing potential, willingness to avoid a pregnancy during the treatment period and for at least 4 weeks from the last dose of drug and utilization of an efficient method of birth control for the entire duration of the trial and until the first menses after a 30-day period after the last dose of trial medication.

Exclusion Criteria:

  • Crohn's disease and indeterminate colitis.
  • Current or previous (in the last 10 days preceding the screening) use of systemic corticosteroids.
  • Use of systemic antibiotics in the last 10 days preceding the screening.
  • Use of systemic Nonsteroidal anti-inflammatory drugs on a repeat basis in the last 10 days preceding the screening.
  • Use of probiotics started within 10 days preceding the screening. A stable regimen from at least 10 days prior to screening is allowed but the patient must be willing to continue up to the end of the study.
  • Use of immunosuppressants or biological agents within the last 6 weeks preceding the screening.
  • Treatment with L-carnitine or its esters derivatives within the last 3 months.
  • Stool culture positive for enteric pathogens (eg, Shigella, Salmonella, Yersinia, Campylobacter) or toxins (C.difficile).
  • Significantly impaired liver, renal, pulmonary or cardiovascular function as assessed by the investigator.
  • History of colon resection.
  • Diverticulitis, symptomatic diverticulosis.
  • Active peptic ulcer disease.
  • Proctitis (extent of inflammation < 15 cm from the anus).
  • Bleeding disorders
  • Rectal therapy with any therapeutic enemas or suppositories with the exception of those required for endoscopy during the 10 days preceding the screening.
  • Active or chronic infection(s) or malignancies.
  • Known hypersensitivity to the active ingredient and excipients of the study drug
  • Patients treated with L-Carnitine or its esters derivatives during the 3 months preceding the screening phase.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Propionyl-L-Carnitine
Modified release tablets containing 500 mg of propionyl-L-carnitine
Drug: Propionyl-L-Carnitine
500 mg modified release tablets, 500 mg bid; treatment duration 8 weeks
Placebo Comparator: Placebo
Modified release tablets containing inert substances
Drug: Placebo
500 mg inert substances modified release tablets, 500 mg bid; treatment duration 8 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of clinical/endoscopic remissions
Time Frame: End of treatment (week 8)
Remission will be defined according with the overall modified Mayo score (Disease Activity Index). A score ≤ 2 with rectal bleeding sub-score = 0 and no other individual sub-score >1 will be considered necessary to classify the patient in remission state.
End of treatment (week 8)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in Rectal bleeding evaluation
Time Frame: At week 2, 6 and 8 of treatment and after 4 week follow-up
Evaluation will be performed by means of Disease Activity Index (DAI) sub-score (from 0 to 3).
At week 2, 6 and 8 of treatment and after 4 week follow-up
Change from baseline in stool frequency evaluation
Time Frame: At week 2, 6 and 8 of treatment and after 4 week follow-up
Evaluations will be performed by means of Disease Activity Index (DAI) sub-score (from 0 to 3).
At week 2, 6 and 8 of treatment and after 4 week follow-up
Histological response to the treatment
Time Frame: End of treatment (week 8)
Evaluated as an improvement of the histological index of at least 1 point
End of treatment (week 8)
Change from baseline in C-reactive protein (CRP) and Fibrinogen
Time Frame: End of the treatment (week 8) and after 4 week follow-up
End of the treatment (week 8) and after 4 week follow-up
Improvement of patients quality of life
Time Frame: End of treatment period (week8) and after 4 week follow-up
A validated specific questionnaire, the SIBDQ by McMaster university will be administered to evaluate changes in patients' quality of life
End of treatment period (week8) and after 4 week follow-up
Haematology
Time Frame: Baseline and end of treatment (week8)
Haemoglobin, Haematocrit, RBC, WBC and differential count.
Baseline and end of treatment (week8)
Electrocardiogram
Time Frame: At baseline and at the end of treatment period (week8)
Standard intervals (PR, RR, QRS, QT) will be collected plus all rhythm abnormalities
At baseline and at the end of treatment period (week8)
Adverse Events collection
Time Frame: 12 weeks
12 weeks
Serum Chemistry
Time Frame: At baseline and at the end of treatment period (week8)
Standard evaluation including renal and liver function, electrolytes and blood glucose
At baseline and at the end of treatment period (week8)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
sigma-tau i.f.r. S.p.A.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
PRA Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Sandro Ardizzone, MD, Head of Inflammatory Bowel Diseases Unit Hospital "Luigi Sacco" Milan - ITALY

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 28, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 30, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ST261DM11006
  • 2011-004770-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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