- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07566884
Safety and Tolerance of a Novel Three-Strain Probiotic in Healthy Adults
A Two-Phase Study on the Safety and Tolerance of a Novel Probiotic in Healthy Adults: Open-Label and Double-Blind, Placebo-Controlled Study
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
A Two-Phase Study safety and tolerance study:
Phase I: Open-Label Study Phase II: Randomised Double-Blind, Placebo-Controlled Study
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Cork, Irlanda
- Atlantia Clinical Trials
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
To be eligible for inclusion, the Participant must fulfill all the following criteria:
- Be able to give written informed consent.
- Be between 18 and 65 years, inclusive.
- Has a BMI: Phase I ≤29.9kg/m2. Phase II ≤34.9kg/m2.
- Mean total food craving score (FCI-UK) of ≥2.5 at screening visit. (Phase I only) 5. Stable weight for the past 30 days (defined as ± 2.3kg).
6. Willing to consume the Study Product daily for the duration of the study.
Exclusion Criteria:
Participants will be excluded from the study if they meet any of the following criteria:
- Participants who are pregnant or wish to become pregnant during the study or who are lactating and/or currently breastfeeding.
Participants currently of biological childbearing potential, but not using a continuous effective method of contraception, as outlined below:
- Complete abstinence from intercourse two weeks prior to administration of the Study Product, throughout the clinical study, until the completion of follow-up procedures or for two weeks following discontinuation of the Study Product in cases where Participant discontinues the study prematurely. (Participants utilising this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding two weeks when they present to the clinic for the final visit).
- Has a male sexual partner who is surgically sterilised prior to the Screening Visit and is the only male sexual partner for that Participant.
- Sexual partner(s) is/are exclusively female.
- Use of acceptable method of contraception, such as a spermicide, mechanical barrier (e.g., male condom, female diaphragm), tubal ligation, or contraceptive pill. The Participant must be using this method for at least one week prior to and one week following the end of the study.
- Use of any intrauterine device (IUD) or contraceptive implant. The Participant must have the device inserted at least two weeks prior to the first screening visit, throughout the study, and two weeks following the end of the study.
Has food allergies or other issues with foods that would preclude intake of the Study Products.
- Known hypersensitivity to any component of the probiotic used in the study (Clostridium butyricum WB-STR-0006, Akkermansia muciniphila WB-STR-0001, Bifidobacterium infantis, chicory inulin, microcrystalline cellulose, l-leucine, hypromellose (vegetarian capsule), silica)
- Known hypersensitivity or allergy to any component of the meal product used in the meal challenge (allergens: milk and soy)
- Has any significant acute or chronic coexisting health conditions that would prevent them from fulfilling the study requirements, put the Participant at risk or would confound the interpretation of the study results as judged by the investigator on the basis of medical history and routine laboratory test results. Excluded health conditions include: a. Gastrointestinal condition (including GI bleeding in the past 3 months) b. Major gastrointestinal surgery or explorations (cholecystectomy and appendectomy are allowed) c. Cancer (in the past 1 year) d. Active autoimmune condition e. Cardiovascular disease (in the past 3 months) 5. Current or recent use of a medication that the investigator believes would interfere with the objectives of the study or pose a safety risk or confound the interpretation of the study results. Prohibited medications include: a. Oral antibiotics or Antifungals (in the past 1 month) b. Medications impacting gut motility (in the 2 weeks prior to baseline) c. GLP-1 receptor agonists (in the past 6 months) d. Sulfonylureas (in the past 6 months) e. Proton Pump Inhibitors (in the past 1 month) f. Laxatives (in the past 1 month)
6. Current or recent (in the past 1 month) use of prohibited nutritional or non-nutritional supplements, including:
- Probiotics/Prebiotics
Fibre supplements 7. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the study.
8. Participants may not be receiving treatment involving experimental drugs/supplements. If the Participant has been in a recent experimental study, these must have been completed not less than 90 days for drugs and 30 days for supplements prior to this study.
9. Current participation or planned participation in a weight loss program during the study period 10. Known hypersensitivity to >4 first-line antimicrobial therapies against Akkermansia muciniphila: Penicillin, Piperacillin, Amoxicillin, Ampicillin, Tetracycline 11. Known hypersensitivity to >4 first-line antimicrobial therapies against Clostridium butyricum: Penicillin, Piperacillin, Amoxicillin, Ampicillin, Tetracycline, Vancomycin, Cefoxitin 12. Known hypersensitivity to >4 first-line antimicrobial therapies against Bifidobacterium infantis Bi-26TM: Gentamicin, Kanamycin, Streptomycin, Tetracycline, Erythromycin, Clindamycin, Ampicillin, Vancomycin
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador activo: Phase 1 - Standard Dose
1 capsule
|
≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
|
|
Comparador activo: Phase 1 - High Dose
2 capsules
|
≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
|
|
Comparador activo: Phase 2 - Active
Dose selected from Phase 1
|
≥ 500 million AFU of Clostridium butyricum strain WB-STR-0006, Akkermansia muciniphila strain WB-STR-0001, Bifidobacterium infantis Bi-26TM, 174 mg chicory inulin (prebiotic), 19mg Microcrystalline Cellulose MCC, 4mg L-Leucine, and 3mg Silica (excipients) to be taken once daily with food
|
|
Comparador de placebos: Phase 2 - Placebo
|
Phase 2 - Matching Placebo
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1 - Safety and Tolerability - As assessed by Occurrence of Adverse of Events
Periodo de tiempo: 8 weeks
|
Phase I: To evaluate the safety and tolerability of 8-week daily supplementation of high-dose versus standard dose Three-Strain Probiotic as assessed by Occurrence of any Adverse Events Change from baseline to week 8.
|
8 weeks
|
|
Phase 2 - Safety and Tolerability - As assessed by Occurrence of Adverse of Events
Periodo de tiempo: 8 weeks
|
Phase 2: To evaluate the safety and tolerability of 8-week daily supplementation of the selected dose (from Phase I) Three-Strain Probiotic as assessed by Occurrence of any Adverse Events Change from baseline to week 8
|
8 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1 - Safety - Blood Biomarkers - Red Blood Cell Count
Periodo de tiempo: 8 weeks
|
(10e12/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - White Blood Cell Count
Periodo de tiempo: 8 weeks
|
(10e9/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Hemoglobin
Periodo de tiempo: 8 weeks
|
(g/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Alanine Aminotransferase
Periodo de tiempo: 8 weeks
|
(IU/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Aspartate Aminotransferase
Periodo de tiempo: 8 weeks
|
(IU/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Serum Creatinine
Periodo de tiempo: 8 weeks
|
(umol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - eGFR
Periodo de tiempo: 8 weeks
|
(mL/min/1.73 m²)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Sodium
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Potassium
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Total Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - LDL Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - HDL Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio
Periodo de tiempo: 8 weeks
|
(no units)
|
8 weeks
|
|
Phase 1 - Safety - Blood Biomarkers - Fasting Glucose
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 1 - Vital signs - Systolic Blood Pressure
Periodo de tiempo: 8 weeks
|
mmHG
|
8 weeks
|
|
Phase 1 - Vital signs - Diastolic Blood Pressure
Periodo de tiempo: 8 weeks
|
mmHG
|
8 weeks
|
|
Phase 1 - Vital signs - Heart Rate
Periodo de tiempo: 8 weeks
|
bpm
|
8 weeks
|
|
Phase 1 - Vital signs - Temperature
Periodo de tiempo: 8 weeks
|
˚C
|
8 weeks
|
|
Phase 1 - Total Food Cravings - Food Cravings Inventory (FCI-UK)
Periodo de tiempo: 8 weeks
|
The Food Craving Inventory (FCI-UK) is a UK-specific version of the Food Craving Inventory designed to measure the frequency of cravings for specific foods over the past month.
The questionnaire lists 27 food items and generates total food cravings scores.
|
8 weeks
|
|
Phase 1 - Food Cravings - Food Cravings Questionnaire-Trait-reduced (FCQ-T-r)
Periodo de tiempo: 8 weeks
|
The Food Cravings Questionnaire- Trait- reduced (FCQ-T-r) is a 15-item reduced version of the Food Cravings Questionnaire (FCQ).
Items included in the FCQ-T-r from the original version subscales include lack of control overeating (5 items), thoughts or preoccupation with food (5 items), intentions and plans to consume food (2 items), emotions before or during food craving (2 items), and cues that may trigger food craving (1 item).
Participants indicate on a 6-point scale from 'never/not applicable to always' how frequently each of the 15 statements relating to food cravings is true for them.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Plasma GLP-1 (Total)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in pg/ml.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Plasma Glucose
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in mmol/L.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Satiety (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Hunger (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Fullness (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 1 - Meal Tolerance Test - Desire to eat (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 1 - Weight
Periodo de tiempo: 8 weeks
|
kg
|
8 weeks
|
|
Phase 1 - BMI
Periodo de tiempo: 8 weeks
|
kg/m2
|
8 weeks
|
|
Phase 2 - Vital signs - Systolic Blood Pressure
Periodo de tiempo: 8 weeks
|
mmHG
|
8 weeks
|
|
Phase 2 - Vital signs - Diastolic Blood Pressure
Periodo de tiempo: 8 weeks
|
mmHG
|
8 weeks
|
|
Phase 2 - Vital signs - Heart Rate
Periodo de tiempo: 8 weeks
|
bpm
|
8 weeks
|
|
Phase 2 - Vital signs - Temperature
Periodo de tiempo: 8 weeks
|
˚C
|
8 weeks
|
|
Phase 2 - Total Food Cravings - Food Cravings Inventory (FCI-UK)
Periodo de tiempo: 8 weeks
|
The Food Craving Inventory (FCI-UK) is a UK-specific version of the Food Craving Inventory designed to measure the frequency of cravings for specific foods over the past month.
The questionnaire lists 27 food items and generates total food cravings scores.
|
8 weeks
|
|
Phase 2 - Food Cravings - Food Cravings Questionnaire-Trait-reduced (FCQ-T-r)
Periodo de tiempo: 8 weeks
|
The Food Cravings Questionnaire- Trait- reduced (FCQ-T-r) is a 15-item reduced version of the Food Cravings Questionnaire (FCQ).
Items included in the FCQ-T-r from the original version subscales include lack of control overeating (5 items), thoughts or preoccupation with food (5 items), intentions and plans to consume food (2 items), emotions before or during food craving (2 items), and cues that may trigger food craving (1 item).
Participants indicate on a 6-point scale from 'never/not applicable to always' how frequently each of the 15 statements relating to food cravings is true for them.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Plasma GLP-1 (Total)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in pg/ml.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Plasma Glucose
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in mmol/L
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Plasma GLP-2
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in pg/ml.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Peptide YY
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in pg/ml.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Plasma Insulin
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
Measured in pg/ml.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Satiety (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Hunger (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Fullness (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 2 - Meal Tolerance Test - Desire to eat (VAS)
Periodo de tiempo: 8 weeks
|
Meal Tolerance Test - initiated in the fasting state with samples collected at T0 (fasting), T30, T60, T90, T120 & T180 mins following a standardised meal.
VAS scales follow 0-100 measurement.
|
8 weeks
|
|
Phase 2 - Weight
Periodo de tiempo: 8 weeks
|
kg
|
8 weeks
|
|
Phase 2 - BMI
Periodo de tiempo: 8 weeks
|
kg/m2
|
8 weeks
|
|
Phase 2 - Hormonal Health - Leptin
Periodo de tiempo: 8 weeks
|
pg/ml
|
8 weeks
|
|
Phase 2 - Hormonal Health - Ghrelin
Periodo de tiempo: 8 weeks
|
pg/ml
|
8 weeks
|
|
Phase 2 - Inflammation - IL-6
Periodo de tiempo: 8 weeks
|
pg/ml
|
8 weeks
|
|
Phase 2 - Inflammation - IL-17
Periodo de tiempo: 8 weeks
|
pg/ml
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Red Blood Cell Count
Periodo de tiempo: 8 weeks
|
(10e12/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - White Blood Cell Count
Periodo de tiempo: 8 weeks
|
(10e9/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Hemoglobin
Periodo de tiempo: 8 weeks
|
(g/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Alanine Aminotransferase
Periodo de tiempo: 8 weeks
|
(IU/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Aspartate Aminotransferase
Periodo de tiempo: 8 weeks
|
(IU/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Serum Creatinine
Periodo de tiempo: 8 weeks
|
(umol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - eGFR
Periodo de tiempo: 8 weeks
|
(mL/min/1.73 m²)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Sodium
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Potassium
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Total Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - LDL Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - HDL Cholesterol
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - LDL:HDL Cholesterol Ratio
Periodo de tiempo: 8 weeks
|
(no units)
|
8 weeks
|
|
Phase 2 - Safety - Blood Biomarkers - Fasting Glucose
Periodo de tiempo: 8 weeks
|
(mmol/L)
|
8 weeks
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Noel Caplice, MD, APC Microbiome Ireland
- Director de estudio: Adam Perlman, MD, MPH, Pendulum Therapeutics, Inc
Publicaciones y enlaces útiles
Publicaciones Generales
- Belzer C, de Vos WM. Microbes inside--from diversity to function: the case of Akkermansia. ISME J. 2012 Aug;6(8):1449-58. doi: 10.1038/ismej.2012.6. Epub 2012 Mar 22.
- Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006.
- Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001319. doi: 10.1136/bmjdrc-2020-001319.
- Huber H, Schieren A, Holst JJ, Simon MC. Dietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions - a narrative review. Am J Clin Nutr. 2024 Mar;119(3):599-627. doi: 10.1016/j.ajcnut.2024.01.007. Epub 2024 Jan 11.
- Yoon HS, Cho CH, Yun MS, Jang SJ, You HJ, Kim JH, Han D, Cha KH, Moon SH, Lee K, Kim YJ, Lee SJ, Nam TW, Ko G. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021 May;6(5):563-573. doi: 10.1038/s41564-021-00880-5. Epub 2021 Apr 5.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- PDL-25-01P - AFCRO-181
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .