Ulcerative colitis is an inflammatory disease that affects the colon. The extent and severity of the disease may vary: it is possible that the disease only the rectum (the lower part of the colon) found, but the disease may extend over the entire…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be the clinical/endoscopic remission defined as a
Disease Activity Index at the end of treatment <= 2 with rectal bleeding
sub-score = 0 and no other individual sub-score >1.
Secondary outcome
Secondary endpoints will be:
• Rectal bleeding evaluation by means of DAI sub-score (from 0 to 3).
• Stool frequency evaluation by means of DAI sub-score (from 0 to 3).
A clinical response for each of these parameters is defined as a sub-score
improvement of at least 1 point over baseline.
The histological response to the treatments, defined as an improvement of the
Histological Index (HI - see Appendix III) of at least 1 point at the end of
the study (a final HI score smaller of equal to 1 will be defined as a
histological remission) will also be evaluated as additional exploratory
end-point.
The serum C-reactive protein and Fibrinogen will be monitored to investigate
possible correlation between clinical/endoscopic outcome and serum level of
these inflammatory markers.
A validated specific questionnaire, the SIBDQ by McMaster University, will be
administered to evaluate changes in patients* Quality of Life.
The safety and tolerability of the treatments will be investigated through AEs
recording, vital signs, ECG and laboratory evaluation.
Background summary
The drug propionyl-L-carnitine hydrochloride is since 1998 marketed under the
name dromos ® (tablets or powder for injection) for the indication of occlusion
of the arterial blood vessels of the lower limbs and chronic heart failure
(improvement of cardiac activity). The active ingredient in the drug's dromos
of propionyl-L-carnitine hydrochloride, a substance that normally the human
body itself produces. The drug propionyl-L-carnitine hydrochloride is used in
this study, is given in the form of a new formulation of modified release
tablets (tablets that selectively dissolve in the colon). This new formula has
been administered to patients suffering from mild to moderate ulcerative
colitis to the positive effects of safety and efficacy testing versus placebo.
Study objective
Ulcerative colitis is an inflammatory disease that affects the colon. The
extent and severity of the disease may vary: it is possible that the disease
only the rectum (the lower part of the colon) found, but the disease may extend
over the entire length of the colon.
Ulcerative colitis is one of the "inflammatory diseases of the gut," a generic
term used to refer to a group of chronic inflammatory diseases of unknown
origin and which affect the intestinal tract.
Generally known patients suffering from ulcerative colitis periods of relapse
(worsening of inflammation) alternating with periods of disease remission.
During relapse, symptoms such as abdominal pain, diarrhea and rectal bleeding
worse.
During remission take these symptoms. In general, remissions for after using
drugs or surgery, but occasionally they can occur spontaneously.
Since there are currently no drugs that can cure ulcerative colitis, is to a
drug treatment to achieve the following: remission induction, and retain the
quality of life of the patient improved.
Medicines used for this standard are as follows: anti-inflammatory drugs such
as 5-aminosalycilzuurverbindingen (5-ASA), corticosteroids and immunomodulators.
Ulcerative colitis can be mild, moderate or severe forms occur, depending on
the clinical, endoscopic (direct observation of the intestinal tract) and
histological (microscopic analysis of intestinal tissue) observations. This
difference determines the most appropriate therapeutic choice for each patient.
The object of this clinical study is whether the administration of
investigational drug propionyl L carnitine hydrochloride can lead to improved
lighting of the disease in patients with mild ulcerative colitis and who are
already treated with a standard drugs (excluding corticosteroids and
immunomodulators). With the research described below, we especially want to
collect data on the efficacy and tolerability of propionyl-L-carnitine
hydrochloride.
This study is "controlled versus placebo ', ie a group of patients receives a
substance which has no pharmacological effect. The use of a placebo is
methodologically necessary to the possible beneficial effects of the
investigational drug to correctly evaluate without bias from external factors.
The primary objective of this study is to compare the two treatment groups
(propionyl-L-carnitine hydrochloride (ST 261) tablets of modified release 1 g /
day vs.. Placebo) with respect to the number of patients with disease remission
at the end of 8 weeks of treatment. Evaluation of the safety and tolerability
of ST 261 is a primary objective of the study.
The secondary objectives are the maintenance of remission after treatment four
weeks was interrupted, the histological changes, improving the symptoms of the
disease (subscores) and the overall quality of life as measured using the Short
Inflammatory Bowel Disease Questionnaire (SIBDQ).
Study design
This study is carried out in 'parallel' groups, ie patients in the study
treated with only one of two different treatments.
This study is a 'double blind' study, this means that neither the patient nor
the clinical investigator knows which treatment the patient has been assigned.
They will only know this when the investigation is complete, but nevertheless,
there is guaranteed that, if necessary, it is possible to immediately find out
which treatment was given. The 'blind' condition is ensured by the fact that
the placebo tablets look similar when the drug under investigation, but the
placebo tablets contain no active ingredient.
This study is a randomized 'study: ie the assignment of one of the two
treatment groups based on random, statistical criteria that are not affected by
the physician nor the patient condition. The chance that one of the two
treatment groups is assigned is the same.
Intervention
See "Description and assessment of strain and risk"
Study burden and risks
If the patient decides to participate in the study, then in this research
study, administration of these treatments provide:
• 1 g of propionyl L-carnitine hydrochloride per day by mouth (orally);
• 1 g placebo daily by mouth (orally).
The chance that one of the two study treatments provided is given is about
50/50.
All patients will be 8 weeks long to take 2 tablets daily (one morning and one
evening), regardless of the treatment group to which they belong.
The study lasts 12 weeks (a treatment for 8 weeks and 4 weeks without
treatment).
The following procedures, the patient underwent
If the patient agrees to participate in this study, under he / she performs an
initial check to determine whether his / her condition matches the criteria for
the study. During that inspection, the investigator or authorized person of the
medical staff his / her questions about his / her medical history. During the
audit, he / she is a thorough investigation, including the following:
• a blood sample of 11 ml;
• give a urine sample;
• a medical examination including measurement of your vital signs (blood
pressure, weight, height, heart rate);
• an endoscopic examination of the large intestine (using a rectal scope),
including four biopsies will be taken (small pieces of the wall of the
intestine for microscopic examination);
• an electrocardiogram;
• in women of childbearing age, there will be a blood test be performed to
exclude a pregnancy;
• it will make him / her ask for a questionnaire consisting of 10 questions
that assessed the quality of life.
If he / she meet the criteria for inclusion in the study, then he / she gets an
electronic device (electronic diary) which is similar to a smartphone. He / she
will receive instructions for this and they will ask him + her all day to write
down the following information:
• Frequency of bowel movements per day (number of bowel movements);
• presence of blood in the stool;
• number of tablets taken.
Furthermore, the patient is given a box containing the active drug or placebo
that hij.zij twice a day, before breakfast and before dinner, orally should
take. Each box contains 4 blisters of 8 tablets each, a total of 32 tablets for
treatment for 14 days (two weeks) plus 2 additional days (if necessary).
After 2 weeks, the patient investigator of another 2 boxes for a further 4
weeks of treatment plus 4 additional days. When the patient to the hospital at
week 6 comes back before the planned visit, he / she is the last box for
treatment of two weeks plus two extra days. At each visit (weeks 2, 6 and 8)
will be him / her ask any unused tablets to the researcher to return.
Apart from the first control mentioned above, are for the study with 4
additional visits after 2, 6, 8 and 12 weeks will take place.
During these visits take place the following controls:
• a blood sample of 11 ml (at 2 and 8 weeks, and only after 12 weeks for any
abnormal values **to follow);
• give a urine sample (at 2 and 8 weeks, and only after 12 weeks for any
abnormal values **to follow);
• a medical examination at all visits, including monitoring your vital signs
(blood pressure, weight, height, heart rate);
• an endoscopic examination of the large intestine (using a rectal scope),
including four biopsies will be taken (only after 8 weeks);
• an electrocardiogram (at 2 and 8 weeks, and only after 12 weeks for any
abnormal values **to follow);
• a questionnaire on the quality of life (after 8 and 12 weeks);
• women of childbearing age, a blood test will be performed to rule out a
pregnancy (after 12 weeks [follow-up visit]).
Since the blood and urine samples for analysis to an external, central
laboratory (Esoterix, Mechelen, Belgium) will be sent, it may be that the
physician for additional samples ask if he / she sees fit if the blood and
urine samples lost or damage which would hit some incorrect values **could be
determined.
Viale Shakespeare 47
Rome 00144
IT
Viale Shakespeare 47
Rome 00144
IT
Listed location countries
Age
Inclusion criteria
1. Have read the Information for the Patient and signed the Informed Consent Form.
2. Age comprised between 18 and 75 included.
3. Diagnosis of active ulcerative colitis confirmed endoscopically (pancolonoscopy) and histologically. A new pancolonoscopy is required if documented evidence of having performed it within the previous 12 months is not available. If available, only a new partial colonoscopy for the visualization of the affected part of the colon is required for the evaluation of the baseline DAI score.
4. Rectal bleeding and stool frequency sub-scores have to be evaluated in occasion of the first patient*s screening study visit (on the basis of the patient*s memory of the episodes occurred during the previous two weeks, and considering the worst condition). At this time the rectal bleeding score must be at least 1. 
These two sub-scores will be re-evaluated (according to a paper diary recording) during the three days preceding the preparation for the baseline (pre-treatment) partial colonoscopy, to be performed as closest as possible to the conclusion of the screening period. 
Sub-scores recorded in occasion of the baseline (pre-treatment) partial colonoscopy will be utilised for the calculation of the baseline Disease Activity Index (DAI) score.
At this time, patients are considered suitable for randomization if they have a Disease Activity index comprised between 3 and 6 inclusive (mild ulcerative colitis), with a rectal bleeding sub-score of at least 1.
5. Stable background oral aminosalycilates (mesalazine, balsalazide, olsalazine) or sulfasalazine standard therapy for greater than or equal to 4 weeks prior to screening assessments.
6. If female, not pregnant or nursing.
7. For women of childbearing potential (WOCBP), willingness to avoid a pregnancy during the treatment period and for at least 4 weeks from the last dose of drug.
A WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilisation (hysterectomy, bilateral tubal ligation or bilateral ovariectomy) or is not postmenopausal (defined as amenorrhoea >12 consecutive months). 
WOCBP should use 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. They must be on a stable regimen, for at least 1 month, of oral contraceptives, contraceptive implant or depot injection, contraceptive patch, intrauterine device (IUD), or condom and spermicidal agent. The patient will be informed about the results of the pregnancy test and of the allowed method of contraception and its duration.
Exclusion criteria
1. Crohn*s disease and indeterminate colitis.
2. Current or previous (in the last 10 days preceding the screening) use of systemic corticosteroids.
3. Use of systemic antibiotics in the last 10 days preceding the screening.
4. Use of systemic NSAIDs on a repeat basis in the last 10 days preceding the screening.
5. 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.
6. Patients previously treated with biological agents have to be excluded, as well as patients treated with immunosuppressants within the last 6 weeks preceding the screening.
7. Stool culture positive for enteric pathogens (eg, Shigella, Salmonella, Yersinia, Campylobacter), Parasites (i.e. Amoebae, Coccidia, Giardia, Helminths) or toxins (C.difficile).
8. Significantly impaired liver, renal, pulmonary or cardiovascular function as assessed by the investigator.
9. History of colon resection.
10. Diverticulitis, symptomatic diverticulosis.
11. Active peptic ulcer disease.
12. Proctitis (extent of inflammation <15 cm from the anus).
13. Bleeding disorders (alterations of the coagulation factors or any concurrent other disease possibly causing digestive apparatus bleeding).
14. Rectal therapy with any therapeutic enemas or suppositories with the exception of those required for endoscopy during the 10 days preceding the screening.
15. Active or chronic infection(s) or malignancies.
16. Known hypersensitivity to the active ingredient and excipients of the study drug. 
17. Simultaneous participation in another clinical trial, or participation in any clinical trial involving investigational drugs within 3 months from enrolment into the present study.
18. Any physical or psychological condition in a patient that could let the investigator suspect his/her poor compliance.
19. Patients treated with L-carnitine or its esters derivatives during the three months preceding the screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-004765-32-NL |
| CCMO | NL39147.058.12 |