Mexico. D.f., Mexico
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Study to evaluate HZN-825 in patients with Diffuse Cutaneous Systemic Sclerosis (dcSSc)
This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial for HZN-825, a selective antagonist of lysophosphatidic acid receptor-1 (LPAR1). Participants will be screened within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio to receive HZN-825 300 mg QD, HZN-825 300 mg BID or placebo for 52 weeks. Participants will take their first dose of trial drug at the clinic and will return to the clinic for trial visits at Week 4 and every 6 weeks thereafter until Week 52. Participants who complete the Double-blind Treatment Period (Week 52) may be eligible to enter a 52-week extension trial (HZNP- HZN-825-302). Participants not entering the extension will return to the clinic for a Safety Follow-up Visit 4 weeks after the last dose of trial drug.
Phase
2Span
139 weeksSponsor
Horizon Therapeutics Ireland DACMexico
Recruiting
A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer
The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC. The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI > 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no). This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.
Phase
3Span
283 weeksSponsor
AstraZenecaMexico City
Recruiting
Curcumin Supplementation in Cervical Cancer
BACKGROUND Cervical cancer (CC) continues to be a major public health problem in Mexico. Today more than 4,000 women die each year from this disease, which requires implementing strategies that can improve current treatments, particularly for locally advanced disease. Today it is clear that persistent high-risk Human Papillomavirus infections are the main risk factor for developing CC. At the National Cancer Institute of Mexico (INCan), 80% of patients are diagnosed at locally advanced stages (IB3-IVA). The standard treatment for these stages is concomitant chemoradiotherapy (CCRT) followed by brachytherapy (BT). p53 restricts tumor growth, promoting cell death and decreasing cell viability. Activation of p53 is vital for CCRT-induced cytotoxicity, while inactivation of p53 has been associated with resistance or insensitivity to treatment. Different nutraceuticals such as berberine and curcumin can reactivate endogenous p53 and exhibit its effects in CC. The E6 oncoprotein inactivates the p53 pathway in CC; therefore, the restoration of p53 may be a promising therapeutic strategy. The health benefits associated with consuming fruits, vegetables, teas, and spices are due to the presence of phytochemicals. Diets characterized by regular consumption of fruits and vegetables have been associated with a decrease in the risk of CC. A particular group of phytochemicals of interest is polyphenols. The polyphenol curcumin is considered safe and non-toxic by the FDA (Food and Drug Administration), and its administration causes minimal low-grade adverse effects (mainly grade 1 diarrhea). Based on clinical trials' safety and toxicity profile, a dose of up to 8000 mg/day of curcumin can be considered safe. The current information on the bioavailability of phytochemicals continues to be limited, which places great importance on the exploration of polyphenols as possible new therapeutics. However, the low bioavailability and complex metabolism linked to polyphenols make it difficult to recommend a dose for daily consumption. The addition of piperine to curcumin supplementation has been demonstrated to increase absorption in the intestine. Different biological effects have been associated with curcumin supplementation in cancer patients. Patients with pancreatic cancer received oral administration of curcumin at a dose of 8 g/day for eight months in combination with gemcitabine, which was well tolerated and showed an improvement in overall survival. Curcumin activity was evaluated in patients with metastatic colon cancer, finding that it was safe and tolerable in combination with FOLFOX. In locally advanced CC patients, the effect that curcumin has on the expression of p53 in tumor cells has not been investigated, although in vitro studies have demonstrated its effect on the inhibition of oncoproteins, such as E6, and the consequent stabilization of p53, which makes CC cells more susceptible to being destroyed. The present pilot study seeks to demonstrate that curcumin supplementation will regulate molecular markers, such as p53 and apoptosis in tumor cells, which could provide the basis to study further whether this modulation by curcumin leads to a greater susceptibility of the tumor to standard cancer treatment and, therefore, a better response to treatment. METHODS The work will be carried out at the National Cancer Institute of Mexico (INCan) in patients with locally advanced CC. Six supplementation groups will be included; in three groups, curcumin will be administered in tablets in oral doses of 1, 3, and 6 g / day respectively, and in the other three groups, curcumin will be administered in tablets in oral doses of 1, 3, and 6 g / day respectively plus 5 mg of piperine/g of curcumin (to facilitate the absorption of curcumin). Invitation to the study protocol: Diagnosis will be confirmed in the INCan Functional Gynecology Oncology Unit. The corresponding studies are carried out to corroborate that the patient meets the inclusion criteria. On the day of the invitation to the patient, the patient will be explained what the study consists of, and the Informed Consents will be read. If the patient agrees to participate and signs the consent, she will be assigned to the corresponding curcumin dose group. The patients will be followed for four visits throughout the study: (1) 2 weeks before the beginning of treatment; (2) at the beginning of CRT; (3) at the third cycle of CRT; and (4) at BT. Patients will be evaluated in 4 visits: - Visit 1: Indications for a standard diet will be given according to the patient's requirements. Curcumin will be provided to the patient, and instructions for its use will be given according to the group to which she has been assigned. Urine and serum samples will be collected. A cervical swab sample will be obtained. - Visit 2: The day of initiation of treatment with concomitant CRT. Feces, urine, and serum samples will be collected. A cervical swab sample will be obtained. - Visit 3: Once the 3 CRT cycles have been completed. Feces, urine, and serum samples will be collected. A cervical swab sample will be obtained. - Visit 4: When starting treatment with BT. Urine and serum samples will be collected. Biological samples: Cervicovaginal cytologies will be taken at each visit. The samples will be analyzed by flow cytometry to quantify p53 positive cells and annexin will be used to identify apoptosis. Adherence to supplementation will be monitored, bioavailability will be investigated, gastrointestinal toxicity determined, and the safety of supplementation evaluated. Gastrointestinal symptoms will be classified at each visit during treatment according to common toxicity criteria (CTCAE v. 5). Liver function tests, renal function tests, blood chemistry, and hematic biometry will be monitored to assess curcumin supplementation safety. Stool, urine, and serum samples will be taken, from which the bioavailability of curcumin will be assessed by liquid chromatography-electrospray ionization-mass spectrometry. A comparative analysis of these variables will be made between the different supplementation groups to establish the dose in which an impact on the expression of p53 and apoptosis is observed. Analysis of data: Data will be analyzed using Statistica software, and graphs will be made in GraphPad Prism. A single-factor repeated measures analysis will be performed with repeated measures across all treatments. The analysis plan will consist of: - Normality test. The Shapiro-Wilk test will be performed to know if the variables' distribution is normal. - Descriptive analysis. The distribution of the quantitative independent variables will be determined using the Kolmogorov-Smirnov test. The mean ± standard deviation will be reported for variables with normal distribution or median with 25th and 75th percentiles for variables with free distribution. - One-way or two-way ANOVA will be performed to determine the significance of differences between groups, followed by Tukey's test for the significance of differences. Confidence intervals will be constructed at 95%, and a value will be declared statistically significant when p is <0.05. - Multivariate analysis. The following tests will be used to determine if there are differences between the patients who were supplemented with the different doses of curcumin and those who also received piperine: - Student's T test for quantitative variables with normal distribution. - Mann Whitney U test for quantitative variables with free distribution or ordinal variables. - Chi-square test for dichotomous and polytomous variables. EXPECTED RESULTS AND PERSPECTIVES The investigators expect that curcumin supplementation will stabilize the expression of p53 and increase the apoptosis of tumor cells. The investigators also expect that piperine will increase its absorption. In addition, a dose in humans associated with the expression of p53 has not been reported, so this study will allow the identification of the dose that favors said expression in humans. In addition to its molecular effect, due to its antioxidant properties, the investigators expect that patients will improve gastrointestinal symptoms associated with treatment with CCRT.
Phase
N/ASpan
102 weeksSponsor
National Institute of CancerologíaMexico City
Recruiting
Ultrasound Guided Diuretic Therapy in Type 1 Cardiorenal Syndrome
Phase
N/ASpan
135 weeksSponsor
Instituto Nacional de Cardiologia Ignacio ChavezMexico City
Recruiting
"Pulmonary Rehabilitation Program in Patients With Interstitial Lung Disease Associated With Systemic Sclerosis"
Consecutive patients who attend the Rheumatology and Internal Medicine services with a confirmed diagnosis of Interstitial Lung Disease associated Systemic Sclerosis, at the Speciality Hospital from the National Medical Center La Raza IMSS, all patients who wish to participate in the study will be asked to sign the informed consent letter from the participating researchers, subsequently the anxiety and depression questionnaire will be applied to them. Goldberg, as well as the SF-36 questionnaire to evaluate quality of life and the SySQ questionnaire to evaluate functionality, to include these data in the analysis, as well as history of smoking, occupational and environmental exposures to both biomass combustion smoke and inorganic powders, these questionnaires are validated in our population and have been widely used, the data corresponding to the time of evolution of the disease, medications used, comorbidities and levels of antibodies and acute phase reactants will be collected from the clinical records. of each of the participants. All participants (T0) will undergo Forced Spirometry, Carbon Monoxide Diffusion Capacity (DLCO) and Cardiopulmonary Exercise Test. The Pulmonary Function Laboratory of the National Medical Center General Hospital has qualified and trained personnel in performing respiratory function tests, the interpretation of said results will be carried out by the main author (doctoral student) who has a high specialty in Respiratory Physiology and Pulmonary Function Laboratory. Subsequently, the patients will be sent to the Pulmonary Rehabilitation service of the La Raza National Medical Center where they will enter a supervised pulmonary rehabilitation program that consists of 36 sessions, which is equivalent to 12 weeks. At the end of this period (T1), again the respiratory function tests (spirometry, plethysmography, DLCO, arterial blood gases and Cardiopulmonary Exercise Test) as well as the Goldberg, SF-36 and SySq questionnaires. The protocol has been submitted for approval to the National Health Research Committee (CNCI). Study procedures. Every day prior to the start of the work day in the Pulmonary Function Laboratory of the National Medical Center La Raza IMSS, the cleaning and disinfection procedures of the equipment are carried out according to the manufacturer's requirements and the procedures are carried out. calibration, both for volume and flow linearity according to ATS/ERS 2005 standards for flow sensors, as well as linearity calibrations for the gas analyzer and pressure and temperature calibrations of the equipment. Prior to performing the lung function tests, anthropometric measurements will be performed as follows: - Height: with the patient in a standing position, height will be obtained with a wall stadiometer model 206 (Seca GMBH & Co., Hamburg, Germany). This measurement will be carried out by placing the heels together, close to the wall, as well as the calves, buttocks, shoulder blades and head. The head will be positioned by asking the patient to look forward, keeping the lateral canthus of the orbit horizontal in relation to the auditory meatus (Frankfort plane). - Weight: with the patient wearing light clothing, the weight will be obtained using a precision digital scale model 813 (Seca GMBH & Co., Hamburg, Germany). Goldberg Questionnaire for Anxiety and Depression The Goldberg Anxiety and Depression Scale is both a screening test, with healthcare and epidemiological uses, and an interview guide. It is a test that not only guides the diagnosis towards anxiety or depression (or both in mixed cases), but also discriminates between them and measures their respective intensities. The Goldberg Anxiety and Depression Scale contains 2 subscales with nine questions in each: anxiety subscale (questions 1-9) and depression subscale (questions 10-18). The first 4 questions of each subscale (questions 1-4) and (questions 10-13), respectively, act as a precondition to determine whether the rest of the questions should be attempted. Specifically, if a minimum of 2 questions from questions 1-4 are not answered affirmatively, the rest of the questions in the first subscale should not be answered, while in the case of the second subscale it is sufficient to answer affirmatively to one question. between questions 10-13 to be able to proceed to answer the rest of the questions. The cut-off points are 4 or more for the anxiety subscale and 2 or more for the depression subscale, with scores being higher the more serious the problem is (the maximum possible being 9 in each of the subscales). Even when the questions are very clear, the answers only admit dichotomy, so that sometimes, when coincidences of slight intensity are involved, the judgment of a specialist professional is necessary to assess the clinical significance of the answer. SF-36 Questionnaire This questionnaire contains 36 items to measure health in eight dimensions: perception of general health, physical and social functioning, limitations of function due to physical or emotional problems, health, vitality and body pain. For each dimension, items are coded, summed, and transformed into a scale from 0 (worst health) to 100 (best health). The eight dimensions can be reduced to two summary measures, a physical component score (PCS) and a mental component score (MCS). The MCID in brief form 36 (SF-36) has been estimated in patients with rheumatoid arthritis which has been estimated at 20% improvement in baseline score. SySQ Questionnaire. It is a self-administered functionality questionnaire for SSc (Systemic Sclerosis Questionnaire [SySQ]), which assesses the difficulty in carrying out activities of daily living and the intensity and frequency of the symptoms with the greatest functional impact in SSc. This instrument was originally designed in German and has been validated in Spanish by this working group. Include 3 domains concerning activities of daily living, intensity and frequency of symptoms. Three domains in 4 categories: 1) general symptoms; 2) musculoskeletal symptoms; 3) cardiopulmonary symptoms, and 4) symptoms of the digestive tract, which are the main organs affected and represent the greatest impact on the functionality of patients with Ssc. This scale includes an ability to perform an action section (0 = no difficulty, 1 = some difficulty, 2 = some difficulty, 3 = unable to do); another section describes the intensity of the symptoms (0 = no, 1 = mild, 2 = moderate, 3 = very severe), and finally there is a section on the frequency of the symptoms (0 = no, 1 = sometimes, 2 = often, 3 = always). The final score of the scale is calculated by averaging the maximum value obtained in each domain (block of questions) divided by 3 (given that there are 3 domains), and that value goes from 0 (normal functionality) to 3 (minimal functionality). The questionnaire formats will be provided by the pulmonary function laboratory staff to the study participants. Forced spirometry. Spirometry is the main test of respiratory function, it evaluates respiratory mechanics and is the standard for diagnosing bronchial obstruction. The test was performed in accordance with ATS/ERS 2005 standards. Once the patient is prepared for the test, the patient is instructed about the procedure. It is explained to him that he will be sitting (preferably in a fixed chair with arm support), with his trunk upright and his head slightly elevated; He is instructed to place a mouthpiece and a nose clip in his mouth and to perform a maximum inhalation and then an exhalation with an explosive and sustained onset. The maneuver will be carried out in a closed circuit. The patient will be asked to maintain forced expiration for at least 6 seconds until reaching a plateau of at least 1 second. The available equipment is the brand and model Jaeger Sentry Suite Ver. 2.13, IOS, Germany. Carbon monoxide diffusing capacity (DLCO) This test is necessary to evaluate gas transfer, it is necessary to complement the diagnosis and rule out interstitial damage in patients who present restriction of extrapulmonary origin. The test will be performed according to ATS/ERS 2017 standards. The patient will be seated (fixed chair with arm support), with the trunk upright and the head slightly elevated. You will be fitted with a nose clip and asked to breathe into the equipment through a sterile antibacterial mouthpiece. At the beginning, breaths were performed in tidal volume and later, based on residual functional capacity, a maximum expiration was made, until reaching a plateau of 1 second and reaching residual volume. When the residual volume was reached, the valves were activated. The patient was encouraged to perform maximum and rapid inspiration (less than 3 seconds), which reached more than 90% of his vital capacity. He must maintain an apnea for 10 seconds, taking care that there are no leaks or valsalva maneuver. The patient was instructed to make a maximum expiration, but slowly and relaxed, lasting longer than 4 seconds. The time between maneuvers was at least 4 minutes. A minimum of two efforts were completed with acceptability criteria in accordance with ATS/ERS 2017. The available equipment is the brand and model Jaeger Sentry Suite Ver. 2.13, Germany. Exercise test.
Phase
N/ASpan
105 weeksSponsor
Coordinación de Investigación en Salud, MexicoMexico City
Recruiting
Clinical Outcomes of the Gore Synthetic Cornea Device
This is a prospective, single-arm, open-label, multi-center early feasibility clinical study designed to evaluate the clinical outcomes of the GORE Synthetic Cornea Device in the treatment of loss of corneal clarity in patients who are candidates for corneal transplantation. Following procedure, clinical follow up will be scheduled over the course of the study duration (12 months).
Phase
N/ASpan
333 weeksSponsor
W.L.Gore & AssociatesMexico City
Recruiting
Anticoagulant-associated Intracranial Hemorrhage
Study observational. The total number of subjects for this study will be determined by the number of patients with intracranial bleeding associated with anticoagulant therapy on the clinical records. Primary objective: To identify the incidence and prevalence of intracranial bleeding events associated to oral anticoagulant therapy including vitamin k antagonists, factor Xa inhibitors and factor 2a inhibitors. Secondary objective: - To identify mortality related to intracranial bleeding associated with oral anticoagulant therapy, including vitamin K antagonists, factor Xa inhibitors and factor 2a inhibitors. - To identify patients´ characteristics correlated with intracranial hemorrhage associated with oral anticoagulants. - To identify treatment patterns: anticoagulant-associated intracranial bleeding management, including clinical, pharmacological, surgical, and interventional treatments, as well as procoagulant therapies. Sample size Justification / Statistical Analysis: Non probabilistic, incidental reasoned selection. The sample size will be determined by the number of patients with intracranial hemorrhage associated with anticoagulation in the clinical records. All electronic medical records that meet the inclusion criteria will be included in the analysis. Descriptive analysis: Descriptive statistics will be used for demographic and clinical characteristics of the study sample. This will include measures of central tendency (mean, median) and measures of dispersion (standard deviation, range). Analytic (Inferential) analysis: A univariate analysis will take place in order to examine the relationship between demographic and clinical variables with anticoagulation-associated intracranial hemorrhage This will include chi-squared tests for categorical data and T-tests or Mann-Whitney U Tests for continuous data. A multivariable logistic regression analysis will be done to identify independent predictors of intracranial bleeding associated with anticoagulant therapy. The variables to include in the model will be determined by de univariate analysis results. The investigators will consider a p-value under 0.05 for statistical significance.
Phase
N/ASpan
25 weeksSponsor
El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco SuarezMexico City
Recruiting
Amniotic Membrane for Dacryocystorhinostomy
Naso-lacrimal duct obstruction (NLDO) causes epiphora, recurrent dacryocystitis, and skin fistulas. Its incidence increases with age. Dacryocystorhinostomy (DCR) is considered the standard treatment for NLDO. Authors describe similar success rates between external or endoscopic approaches. The former uses a skin approach, through which an osteotomy is made, allowing access to the lacrimal sac and subsequently to the middle meatus of the nasal cavity. On the other hand, endoscopic surgery uses an endonasal route to create a fistula towards the lacrimal sac, with the benefit of not generating visible scars in patients. The success of both surgeries depends on creating a wide osteotomy and the preservation of the mucosa around it, reducing the risk of scarring and stenosis of the ostium formed. Some authors suggest that limiting the inflammatory process localized to the osteotomy may improve the surgical success rate. The use of mitomycin C (MMC) has been reported, with limited results due to variability in the concentration and methods of drug used. Amniotic membrane (AM) has been used in ophthalmology, such as in pterygium surgery, chemical trauma, and inflammatory diseases of the ocular surface. In these contexts, AM limits the inflammatory response, promotes re-epithelialization, and reduces fibrosis. AM epithelial cells do not express HLA-A, B, C, or DR antigens on their surface, and therefore do not present a risk of rejection by the immune system. This study aims to compare the success rate of external DCR with and without amniotic membranes in patients with NLDO.
Phase
1Span
61 weeksSponsor
Instituto de Oftalmología Fundación Conde de ValencianaMexico City
Recruiting
Prevalence of Abuse Among Patients With Rheumatic Diseases
Patients with rheumatic diseases (RD) have a relevant representation in the adult population in Mexico. RD are characterized by their chronic and progressive nature, which can impact functionality during the disease and can present various factors that can be associated with the presence of abuse, among others, economic dependence, decreased physical capacity, and need for care and support in different health processes. In 1970, the phenomenon of abuse in geriatric patients was described for the first time as a phenomenon identified as a public health problem and an issue of human rights violation. In 2012 Giraldo-Rodríguez developed and validated the Geriatric Abuse Scale (GAS), an instrument that, with adequate psychometric properties, reported a prevalence of abuse of 10.28% in Mexico. Regarding abuse in patients with RD, there is little information in the literature; however, it is possible that the prevalence could be similar to that of the occurrence in older adults since both populations share important states of vulnerability. The study aimed to identify the prevalence of abuse in patients with RD. The study will be conducted in two phases: the first one in which the GAS will be adapted for patients with RD, and this version will be validated in a population of our Institute, and the second one in which, applying the validated instrument, the magnitude of abuse is evaluated, and the factors associated with this phenomenon among patients with RD are explored.
Phase
N/ASpan
153 weeksSponsor
National Institute of Medical Sciences and Nutrition, Salvador ZubiranMexico City
Recruiting
Nitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer.
The prognosis of patients with central nervous system (CNS) metastases is poor. About 50% of patients with CPCNP and EGFR mutation have tumor activity in the central nervous system during the first 2 years of diagnosis. Treatment with total cranial radiation therapy (CRT) has shown to have a benefit in local response and patient survival. However, resistance factors such as intratumoral hypoxia decrease the response by CRT. Thus, the use of nitric oxide generators, such as nitroglycerin, has been shown to avoid radio resistance. A previous study conducted at our Institute showed that the addition of transdermal nitroglycerin (NTG) CRT increases intracranial response evaluated by objective radiological response in patients with NSCLC and the subgroup in which a greater benefit was seen was in patients with mutations in the EGFR gene. In this study we propose that the addition of transdermal nitroglycerin to patients with brain metastases and mutations in the EGFR gene receiving CRT will have an increase in intracranial objective response.
Phase
N/ASpan
156 weeksSponsor
Instituto Nacional de Cancerologia de MexicoMexico City
Recruiting