COMPARISON OF THE COMBINED TREATMENT OF THE LIPOSOMATED POLYPHENOLS CÚRCULA AND RESVERATROL® WITH DUTASTERIDE, IN THE IMPROVEMENT OF PATIENTS WITH ELA WHO ARE BEING TREATED WITH RILUZOLE

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2021-001989-38-ES
• Date of registration: 14/06/2021
• Prospective Registration: Yes
• Primary sponsor: Facultad de medicina y ciencias de la salud de la Universidad Católica de Valencia
• Public title: COMPARISON OF THE COMBINED TREATMENT OF THE LIPOSOMATED POLYPHENOLS CÚRCULA AND RESVERATROL® WITH DUTASTERIDE, IN THE IMPROVEMENT OF PATIENTS WITH ELA WHO ARE BEING TREATED WITH RILUZOLE
• Scientific title: IMPACT OF THE COMBINED TREATMENT OF THE LIPOSOMATED POLYPHENOLS CÚRCULA AND RESVERATROL® WITH DUTASTERIDE, IN THE CLINICAL IMPROVEMENT OF PATIENTS WITH ALS TREATED WITH RILUZOLE - IMCRELA
• Date of first enrolment: 08/07/2021
• Target sample size: 100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-001989-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Carlos Barrios
• Affiliation: FACULTAD DE MEDICINA Y CIENCIAS DE LA SALUD DE LA UNIVERSIDAD CATÓLICA DE VALENCIA

• Name: Carlos Barrios
• Affiliation: FACULTAD DE MEDICINA Y CIENCIAS DE LA SALUD DE LA UNIVERSIDAD CATÓLICA DE VALENCIA

Key inclusion & exclusion criteria

Inclusion criteria:
•Male patients over 18 years of age or female patients over 50 years of age who are not fertile, and between 18 and 50 years of age who have accepted the use of contraceptives if they are of childbearing age and renounce becoming pregnant during the intervention.
•Patients diagnosed and symptomatic of ALS for at least 6 months prior to inclusion in the study.
•Patients treated with Riluzole at least one month before inclusion in the study.
•Acceptance of participation in the study by signing the IC form.
•At the discretion of the investigator, the patient must be able to meet the requirements of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
•Patients with tracheostomy.
•Patients with invasive or non-invasive ventilation with positive ventilatory pressure.
•Participation in any other trial or in the 4 weeks prior to inclusion.
•Gastro-stomized patients.
•We are ill with evidence of dementia.
•We are ill with dependence on alcohol or drug abuse.
•Patients infected with hepatitis B or C, or HIV positive.
•Kidney patients with creatinine 2 times higher than normal markers 30 days before inclusion.
9.Hepatic patients with hepatic markers (ALT, AST) elevated 3 times above normal levels 30 days prior to enrollment.
10.Patients treated with anticoagulants or with hemostatic problems 30 days before inclusion.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis
MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Dutasterida
Product Name: Dutasterida
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: DUTASTERIDE
CAS Number: 164656-23-9
Other descriptive name: DUTASTERIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: •Assess activity at the cognitive and behavioral level in ALS patients, and its effects on the quantity and quality of sleep, after the intervention with the combination of Liposomal Turmeric / Resveratrol® with Dutasteride, at baseline visit, 3 and 6 months.
•Quantify the decrease in oxidative stress, after the intervention with the indicated drug combination, at the baseline visit, 3 and 6 months.
•Quantify the possible decrease in inflammation, after the intervention with the indicated drug combination, at a baseline visit, 3 and 6 months.
•Assess the effects on the intestinal microbiota, after the intervention with the indicated drug combination, related to cognitive and behavioral changes at the beginning, 3 and 6 months.
•Assessment of muscle strength and capacity at baseline visit, 3 and 6 months after onset.
•Assessment of the quantity and quality of sleep, after the intervention with the indicated combination of medications, at a baseline visit, 3 and 6 months.

Primary end point(s): Determine functional improvement, understanding as such a statistically significant increase in the mean score obtained on the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRR-R) associated with ALS with respect to the baseline visit, at 3 and 6 months. treatment.

Timepoint(s) of evaluation of this end point: 9 months

Main Objective: To assess the functional improvement of the combined treatment with Liposomal Turmeric / Resveratrol® with Dutasteride in comparison with patients in routine clinical practice

Secondary Outcome(s)

Secondary end point(s): - Motor Variables: The scales and tests carried out will try to determine improvement in muscular and respiratory activity, which deteriorates due to motor neuron damage.
The tests will be the following:
• Electromyography (EMG). Graphic recording technique of the electrical activity produced by skeletal muscles. EMG can be monitored through electrodes inserted into the muscles (intramuscular electrodes) or through electrodes on the surface of the skin over the muscle (superficial electrodes) with the FREE-EMG 300 Electromyograph (8 CHANNELS). This EMG is electromyographic data acquisition and analysis software. In this version, 8 acquisition channels are considered that allow the acquisition of EMG, Switch and / or Force Cell data. The graphical interface is designed for a 1280 x 1024 screen area.
• TEST MRC 11 –steps-mrc grading scale measures muscle strength
• Measurement of forced vital capacity (FVC): FVC is an indicator of lung capacity and would be obtained by performing spirometry, measuring it using a peak expiratory flow meter.
- Variables for cognitive and behavioral assessment: The assessment of cognitive and behavioral functions will try to determine possible improvements in these functions, linked to the damage that occurs in the frontotemporal area of ??the cortex in patients with ALS. To carry out these assessments, the following cognitive and behavioral tests will be applied.
The tests will be:
• Edinburgh ELA Cognitive and Behavioral Exam (ECCE)
• A behavioral test-interview with the caregiver that asks questions with a dichotomous answer Y / N about the presence of uninhibited behavior, apathy or behavioral inertia, lack of sympathy or empathy, perseverative, stereotyped, compulsive or ritualistic behavior, as well as hyperorality and alteration of eating behavior. Likewise, it collects 3 questions about the possible presence of psychotic symptoms.
-Variables related to the microbiota: A Clinical Intestinal Microbiome will be carried out, which is an analysis of the bacterial microbiota present in the intestine, from a stool sample. With this test the improvement will be assessed by the percentage of patients who present a increase of Akkermansia muciniphila, bifidobacterium or lactobacillus (the increase of any of the 3, especially the first); or a decrease in Escherichia coli or Ruminococcus torques (either of the two, but especially the second) at baseline, at 3 months (according to the investigator), and at 6 months.
-Variables related to the quantity and quality of sleep:
• Clinical questionnaire for screening of sleep pathologies, hereinafter, sleep test (TS)
• Measurement through diaries (DS) and scales (ES) of multiple quantitative and qualitative sleep variables (Epworth Test (sleepiness) and Pittsburgh Test (sleep quality)).
-Variables related to inflammation and oxidation:
• Quantitative measurement of plasma IL-6 and TNF-alpha.
• Quantitative measurement of plasma CRP.
• Quantitative measurement of plasma haptoglobin.
• Quantitative assessment of TEAC (oxidation).
• Quantitative measurement of plasma 8-oxoG.
• Quantitative measurement of plasma MDA.

Timepoint(s) of evaluation of this end point: 9 months

Secondary ID(s)

IMCRELA

Source(s) of Monetary Support

FACULTAD DE MEDICINA Y CIENCIAS DE LA SALUD DE LA UNIVERSIDAD CATÓLICA DE VALENCIA

Ethics review

Status: Approved
Approval date: 31/05/2021
Contact: