cyrilzakka/clinical-trials huggingface dataset:
Expanded Access Program for Tofersen in Participants With Superoxide Dismutase 1-Amyotropic Lateral Sclerosis

The objective of this early access program (EAP) is to provide access to tofersen to eligible participants with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene prior to an alternative access mechanism in order to address a high unmet medical need in this population.

Treating healthcare professionals (HCPs) of participants who meet the inclusion/exclusion criteria may request access by emailing medicineaccess@clinigengroup.com. The current EAP structure does not limit participants to receive access at specific sites. Treating HCPs can submit requests on behalf of participants by emailing Clinigen at the email address provided below. Information on the EAP eligibility criteria, including participants and center criteria, will be provided by Clinigen as part of the enrollment request process.

Eligibility Criteria:
Key Inclusion Criteria:

* Medically able to undergo the program procedures, as determined by the treating healthcare professional (HCP).
* Weakness attributable to ALS and associated with a mutation in the SOD1 gene (SOD1-ALS).

Key Exclusion Criteria:

* Previous or current participation in a clinical trial of tofersen.
* Use of an investigational medicinal product (IMP) for amyotrophic lateral sclerosis (ALS) within 5 half-lives of the IMP before the first dose of tofersen.
* Participant's primary place of residence is outside of the country of treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Effects of Standing and Light-intensity Activity on Ambulatory Blood Pressure and Blood Glucose

This study aims to test the short-term effects of intermittent standing, slow cycling and slow walking, compared to sitting, on continuous blood glucose and ambulatory blood pressure among pre-hypertensive and pre-diabetic adults.

This study will enroll 10 adults who will each complete four experimental conditions in random order. Each of the four experimental conditions are as follows: 1) sit continuously for 8 hours in a simulated office environment, 2) break-up sitting time with standing based on set hourly intervals, 3) break-up sitting time with slow-walking on a treadmill desk based on set hourly intervals, 4) increase energy expenditure by slow cycling based on set hourly intervals. Participants will completed each condition one week apart and dietary intake will be standardized by giving participants the same meals during each intervention condition. Study measures will include: anthropometrics (height and weight), blood pressure, fasting glucose, 24-continuous glucose monitoring, full-day ambulatory blood pressure monitoring, cognitive testing (cognitive performance), energy expenditure, physical activity via accelerometer, sleep via accelerometer, and heart rate.

Eligibility Criteria:
Inclusion Criteria:

* pre-hypertensive (systolic blood pressure 120-139 mmHg, or diastolic blood pressure 80-89 mmHg)
* impaired fasting glucose (5.6-6.9 mmil/L)
* not meeting the physical activity guidelines for adults (\>=150 min/wk of moderate-to-vigorous physical activity)

Exclusion Criteria:

* smoking, pregnancy, known coronary heart disease, orthopedic limitations for performing physical activity, taking medications to control high blood pressure or high blood glucose, special dietary requirements, and being advised by a doctor to avoid prolonged periods of sitting.
Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Thrombosis is the main cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in MPN is still largely elusive. Neutrophils can release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". NETs are known to be procoagulant. Our main objective is to quantify NETs biomarkers expression in MPN patients and define if they could be used as prognostic factors in the outcome of thrombosis in these patients.

Myeloproliferative neoplasms (MPN) are acquired clonal hematopoietic stem cell disorders, characterized by an increase in one or more myeloid lineages. The Philadelphia chromosome negative (Ph-) MPN include polycythemia vera (PV) with an excess of red blood cells, essential thrombocythemia (ET) with an increase in platelets and primary myelofibrosis (PMF). Arterial and venous thromboses are the main causes of morbidity and mortality in MPN with reported incidences ranging from 12-39% in PV and 11-25% in ET. The pathogenesis of thrombosis in MPN patients is complex and still largely elusive. The overproduction of neutrophils could be an important risk factor in the thrombus formation. Indeed neutrophils are known to promote thrombosis when they release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". Increased NETosis has been reported in a mouse model of MPN. The main objective of this study is to investigate whether NET biomarkers are associated with increased thrombotic risk in patients with ET. Indeed, an international thrombotic prognostic score has been published in ET, ie the IPSET Thrombosis score (history of thrombosis, age, presence of JAK2V617F, cardiovascular risk factors).

Plasma from MPN patients will be collected, at the time of diagnosis, and measure markers of neutrophil activation, including NET biomarkers. The IPSET Thrombosis score will be evaluated in patients with ET and the correlation between the IPSET Thrombosis score and these biomarkers will be measured.

No follow-up is required for this study.

Eligibility Criteria:
Inclusion Criteria:

* Adults (age ≥18 years),
* Patients diagnosed with Polycythemia vera (PV) or essential thrombocythemia (ET) according to WHO 2008 criteria,
* Affiliated to the national social security system,
* Signed informed consent form will be required for each included subject after having read the information note,
* Patient agreeing to be included in the FIMBANK register and having signed the corresponding consent

Exclusion Criteria:

* Adults (age \>18 years), male or female,
* Patients treated with heparin or undergoing cytoreductive treatment,
* Pregnant or lactating woman,
* Person under guardianship, tutorship or other legal protection scheme or incapable of giving consent
MK0431A Comparative Study in Patients With Type 2 Diabetes (0431A-079)(COMPLETED)

The purpose of this study is to investigate the efficacy and safety of an investigational treatment for type 2 diabetes mellitus.


Eligibility Criteria:
Inclusion Criteria:

* Patient has type 2 diabetes mellitus
* Patient is greater than or equal to 18 and less than or equal to 78 years of age on the day of signing the consent
* Patient has Hb1Ac greater than or equal to 7.5% and is appropriate for oral therapy
* Patient has not been on any antihyperglycemic agent (AHA) in the last 4 months
* Patient is a male, or a female who is unlikely to conceive

Exclusion Criteria:

* Patient has type 1 diabetes mellitus or history of ketoacidosis
CD34+ Selected Stem Cell for Poor Graft Function or Graft Failure

The proposed trial is a single arm, non-randomized, single center pilot study utilizing CliniMACS CD34 Reagent System for patients following allogeneic hematopoietic stem cell transplant (HSCT) requiring treatment of graft dysfunction or failure.

The primary objective of the study is to estimate the incidence of engraftment with sustained recovery of blood counts, including, absolute neutrophil cell (ANC) and platelet engraftment.

* ANC engraftment is defined as ANC of ≥ 0.5 × 10\^9/L for three consecutive laboratory values obtained on different days. Date of ANC recovery is the date of the first of three consecutive laboratory values where the ANC is ≥ 0.5 × 10\^9/L.
* Platelet engraftment should reflect no platelet transfusions administered for seven consecutive days. Report the date of the first of three consecutive laboratory values ≥ 20 × 10\^9/L obtained on different days.

The secondary objective of the study is to estimate the incidence of Graft-versus-host disease (GvHD) and side effects that can be attributed to the CliniMACS CD34 Selected Cellular Product.

Eligibility Criteria:
Inclusion Criteria:

* Recipient of allogeneic transplantation, adult ≥18 years, from any type of donor including matched related, matched unrelated, mismatched related or mismatched unrelated or haploidentical donor transplant.
* Documented evidence of graft dysfunction or failure (a-c):

  1. Primary graft Failure: Graft failure is defined as failure to achieve neutrophil engraftment by day +28 or lack of donor chimerism \> 50% by day 45 not due to the underlying malignancy;
  2. Poor graft function is defined by at least 2 of the following 3 criteria: Hemoglobin \< 8 g/dL, ANC \< 0.5x109/L, and platelets \< 20x109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to hematopoietic growth factors and must last at least 4 weeks;
  3. Secondary graft failure is defined as poor graft function associated with donor chimerism \< 5% after initial engraftment
* Transplanted donor availability
* Negative pregnancy test within seven (7) days of product infusion for women of childbearing potential.

Exclusion Criteria:

* Graft failure due to disease relapse or evidence of disease relapse or progression
* Donor unavailable or unable to collect peripheral HPC by apheresis
* Responsive to conventional measures (such as, hematopoietic growth factor)
* Allergic reaction to murine proteins or iron dextran
* Women of childbearing potential with positive serum HCG
Mitochondrial-targeted Antioxidant Supplementation for Improving Age-related Vascular Dysfunction in Humans

The majority of cardiovascular diseases (CVD) occur in men and women ≥60 years of age. Vascular dysfunction, including endothelial dysfunction, as assessed by reduced endothelium-dependent dilation (EDD), and stiffening of the large elastic arteries (i.e., aortic and carotid artery stiffening), is a major mechanism of increased risk of CVD in older adults. Excess production of ROS (reactive oxygen species) by mitochondria (mtROS) has emerged as a central feature of vascular oxidative stress with aging and driver of age-related vascular dysfunction. As such, identifying novel strategies to decrease mtROS and improve vascular function, to ultimately reduce the risk of age-related CVD, is an important biomedical objective.

MitoQ is a mitochondria-targeted antioxidant that accumulates at the inner mitochondrial membrane where it is optimally positioned to reduce mtROS. Preclinical findings showed that 4 weeks of oral MitoQ supplementation completely restored EDD in old mice, ameliorated mtROS-associated suppression of EDD, and was associated with reduced arterial mtROS, oxidative stress, and improved mitochondrial health. MitoQ therapy also reduced aortic stiffness in old mice. A recent small pilot study of older adults (n=20) found that supplementation with MitoQ was well-tolerated, improved endothelial function, and reduced plasma levels of oxidized low-density lipoprotein, a circulating biomarker of oxidative stress. Consistent with the preclinical findings, preliminary mechanistic assessments in subsets of subjects from the pilot study suggested that improved endothelial function with MitoQ was mediated by reduced endothelial cell mtROS production, associated reductions in tonic mtROS-related suppression of EDD, and improved mitochondrial health, linked in part to changes in circulating factors in the serum induced by chronic MitoQ supplementation. Lastly, MitoQ reduced aortic stiffness in older adults who exhibited age-related aortic stiffening at baseline.

The investigators are conducting a randomized, placebo-controlled, double-blind clinical trial to establish oral MitoQ (20 mg/day; MitoQ, Ltd.) for 3 months vs. placebo (n=56/group) for improving endothelial function in older men and women (≥60 years), and determine the mechanisms by which MitoQ improves endothelial function. The investigators will also assess the effect of MitoQ on aortic stiffness.


Eligibility Criteria:
Inclusion Criteria:

* Age 60 years and over
* Ability to provide informed consent
* Willing to accept random assignment to condition
* Body mass index \<40 kg/m2
* Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study
* Free from alcohol dependence or abuse,
* Mini-mental stage examination score ≥21

Exclusion Criteria:

* Uncontrolled thyroid disease
* Regular vigorous aerobic (\>6 bouts/week, \>60 min/bout at a workload \>6 METS)
* Blood donation within 8 weeks prior to enrolling in the study
Establishing a Diagnostic and Therapeutic Index in Autism Spectrum Disorder (ASD) and Fragile X Syndrome

The purpose of this study is to accumulate and quantitatively analyze data on the microbiome, serotonin signaling and genetics, and inflammatory cytokines from patients with Autism Spectrum Disorder and Fragile X Syndrome. Computational analysis of multi-dimensional datasets will be used to establish a "Diagnostic and Therapeutic Index" - an objective set of tools that can help differentiate subtypes of Autism Spectrum Disorder and develop more accurate methods of diagnosis and response to treatment.


Eligibility Criteria:
Inclusion Criteria:

* Early childhood (pre-diagnosis) OR existing ASD diagnosis (Moderate to Severe)
* Existing FXS diagnosis

Exclusion Criteria:

* Hospitalization
* Enrolled in another clinical study
S9714: Paclitaxel in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy with paclitaxel in treating patients with stage IIIB or stage IV non-small cell lung cancer.

OBJECTIVES: I. Assess survival, progression-free survival and response rate of patients with bronchioloalveolar carcinoma receiving paclitaxel. II. Evaluate toxic effects of paclitaxel in 96 hour continuous infusion patients.

OUTLINE: Patients receive 6 cycles of paclitaxel by IV continuous infusion over 96 hours. Before cycle 4, restaging is performed. If disease progression is witnessed, patients are removed from the study. If a stable, partial, or complete response is observed, patients receive the total of 6 cycles. Three weeks after the last cycle, final restaging is performed. Patients are followed every 3 months while on treatment and every 6 months thereafter, unless more frequent follow-up is clinically recommended.

PROJECTED ACCRUAL: 50 patients will be enrolled. The accrual rate is estimated at 25 per year.

Eligibility Criteria:
DISEASE CHARACTERISTICS: Histologically proven Stage IIIB or IV bronchioloalveolar non-small cell lung carcinoma -incompletely resected or unresectable -tumors may be multifocal or diffuse -measurable or evaluable disease required No prior brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance Status: SWOG 0-2 Life Expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than institutional upper limit of normal (ULN) SGOT no greater than 2 times ULN Renal: Creatinine no greater than institutional ULN OR creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Effective contraceptive method used while on study No prior malignancies allowed, except: basal or squamous cell skin cancer in situ cervical cancer Stage I or II cancer which is in remission Any cancer from which patients have been disease free for 5 years

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for lung cancer Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiation therapy (including palliative radiotherapy) Surgery: Prior surgery is allowed
The CoCoS Interventional Trial: Caloric Control in Cardiac Surgery Patients

Background: Malnutrition is widespread among cardiac surgery patients and is independently related to an adverse postoperative evolution or outcome. The investigators aimed to assess whether nutrition therapy (NT) could alter caloric deficit, morbidity, and mortality in patients scheduled for non-emergency coronary artery bypass graft (CABG) or aortic valve surgery.

Methods: 351 patients undergoing either elective CABG or aortic valve surgery were studied. Patients receiving NT were enrolled from January 2013 until December 2014. A historical control group consisted of 142 matched patients. Preoperative nutritional status was evaluated. Resting energy expenditure was measured using indirect calorimetry or calculated. Caloric intake and caloric deficits were assessed. The primary endpoint was to evaluate whether NT could limit caloric deficit (Intake to Need Deviation). A secondary endpoint addressed the potential effect of NT on morbidity and mortality. Patients were followed for one year after surgery.

Background: Malnutrition, often presenting as sarcopenic obesity, is widespread among cardiac surgery patients and is independently related to an adverse postoperative evolution or outcome. Nutritional status and energetic needs or deficits in cardiac surgery patients are poorly documented and undernutrition, though readily modifiable, is an often overlooked condition during hospitalization. The investigators aimed to assess whether nutrition therapy (NT) could alter caloric deficit, morbidity, and mortality in patients scheduled for non-emergency coronary artery bypass graft (CABG) or aortic valve surgery.

Methods: 351 patients undergoing either elective CABG or aortic valve surgery were studied. Patients receiving NT were enrolled from January 2013 until December 2014. A historical control group consisted of 142 matched patients who underwent either type of surgery. In all patients, the NRS 2002 and MUST score were used for evaluating the preoperative nutritional status. Resting energy expenditure was measured using indirect calorimetry or calculated. A dietician assessed daily caloric intake during the entire hospitalization. Caloric deficits were calculated. According to a predefined flow-chart protocol, nutritional interventions were launched on different time points. Interventions varied from nutritional modifications to oral supplementation, tube feeding, and parenteral nutrition. The primary endpoint was to evaluate whether NT could limit caloric deficit (Intake to Need Deviation). A secondary endpoint addressed the potential effect of NT on morbidity and mortality. Patients were followed for one year after surgery.

Eligibility Criteria:
Inclusion Criteria:

* adult patients scheduled for conventional non-urgent cardiac surgery type coronary artery bypass graft (CABG) or aortic valve surgery

Exclusion Criteria:

* urgent surgery
* aortic arch surgery or other cardiac surgery procedures requiring sternotomy
* off-pump cardiac surgery
* preoperative hemodynamic instability
* pregnancy
Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel

This is an Asia-Pacific regional, randomized, double-blind, multicenter trial designed to evaluate treatment with trastuzumab + pertuzumab + docetaxel compared with trastuzumab + placebo + docetaxel in chemotherapy-naïve participants with early-stage or locally advanced HER2-positive breast cancer. The anticipated treatment duration is approximately 17 months.


Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed invasive breast carcinoma with a primary tumor size of more than (\>) 2 centimeters (cm) by standard local assessment technique
* Breast cancer stage at presentation: early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0)
* HER2-positive breast cancer confirmed by a Sponsor-designated central laboratory and defined as 3+ score by immunohistochemistry in \> 10 percent (%) of immunoreactive cells or HER2 gene amplification (ratio of HER2 gene signals to centromere 17 signals equal to or more than \[\>=\] 2.0) by in situ hybridization
* Known hormone receptor status (estrogen receptor and/or progesterone receptor)
* Eastern Cooperative Oncology Group Performance Status equal to or less than (\<=) 1
* Baseline left ventricular ejection fracture \>= 55% measured by echocardiography (preferred) or multiple gated acquisition scan
* Negative serum pregnancy test

Exclusion Criteria:

* Stage IV metastatic breast cancer
* Inflammatory breast cancer
* Previous anti-cancer therapy or radiotherapy for any malignancy
* History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
* Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
* Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
* Serious cardiac illness or medical condition
* Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
* Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
* Pregnant or lactating