cyrilzakka/clinical-trials huggingface dataset:
Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

Despite good progress during the last decade, hemophagocytic lymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first one, a treatment regimen based on two drugs called etoposide and dexamethasone, has been used worldwide. The second regimen, based on two drugs called Anti-thymocyte globulin (ATG) and prednisone, has been used mostly at one hospital in Paris, for over 15 years. With either regimen, about three quarters of treated children survive the most difficult time, the first two months after diagnosis. These two different regimens appear to work somewhat differently, and we suspect that combining them may give better results than either regimen alone. We are conducting this clinical trial to test the combination of ATG, dexamethasone, and etoposide for the treatment of HLH.

The purpose of this research study is to find out what effects (good and bad) this drug combination has on you and your HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder first recognized almost 70 years ago.(1) Genetic and animal studies have indicated that the familial form of HLH is clearly due to a deficiency of cytotoxic killing. Patients with HLH present with a potentially fatal syndrome of 'hyperimmunity.' These patients have severe inflammation, associated with cytopenias and variably severe bone marrow, liver, or CNS damage. Tissue damage and mortality appear to be due to hypercytokinemia related to persistent immune hyperactivation. An animal model of HLH and correlative human studies all suggest that excessive and abnormal activation of T cells drives the pathophysiology of this disorder, and that suppressing this excessive activation is critical for successful therapy of HLH. It is believed a combination of the two proven induction regimens for hemophagocytic lymphohistiocytosis (HLH) (anti-thymocyte globulin (ATG)- and etoposide-based) will result in response rates and overall survival rates at eight weeks which are comparable or better than the current standard of care (induction therapy per the HLH-94 protocol).

Eligibility Criteria:
Inclusion Criteria:

* diagnosis of hemophagocytic lymphohistiocytosis
* Patients \<18 years of age
* The patient must have active disease at the time of enrollment
* Patient's legal guardians must sign an Institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study.
* Eligible subjects must be enrolled with the protocol coordinating center

Exclusion Criteria:

* Recent treatment, within 3 months, with another therapeutic regimen for HLH
* Known active malignancy
* Known rheumatologic diagnosis which may be the underlying cause of HLH
* Pregnancy (as determined by serum or urine test) or active breast feeding
* Failure to provide signed informed consent
Study of Mogamulizumab + MEDI4736 (Durvalumab) and Mogamulizumab + Tremelimumab in Subjects w/ Advanced Solid Tumors

Mogamulizumab in Combination with MEDI4736 (Durvalumab) and Mogamulizumab in Combination with Tremelimumab in Subjects with Advanced Solid Tumors


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years;
* Locally advanced or metastatic solid tumors;
* Histologically or cytologically confirmed disease;
* Failed or were intolerant to at least one prior systemic treatment regimen with oral or IV medications and have no additional therapy options known to prolong survival with the exception of PD-1 or PD-L1 blockade therapy for subjects who will be enrolled in treatment arm A. Subjects with non-small cell lung cancer must have received at least one platinum doublet regimen. Subjects with known epidermal growth factor receptor tyrosine kinase inhibitor activating mutations or anaplastic lymphoma kinase rearrangement must have also exhausted approved targeted therapy options;
* The subject has a tumor suitable for biopsy and is willing to undergo tumor biopsy, preferably of the primary tumor, within 28 days prior to Cycle 1/Visit Day 1;

Exclusion Criteria:

* Any concurrent chemotherapy, biologic, hormonal, radiation, or investigative therapy for cancer treatment within 21 days prior prior or within 6 weeks prior to Cycle 1/Visit Day 1 for nitrosoureas or mitomycin C;
* Concurrent or prior use of immunosuppressive medication within 28 days;
* Active or prior documented autoimmune, or inflammatory bowel disease, or inflammatory bowel disease. or systemic treatment for psoriasis within the past 5 years.;
* Prior hypersensitivity reaction to monoclonal antibodies, other therapeutic proteins, or immunotherapy.
Efficacy and Safety of Telitacicept in Early SLE

The purpose of this study is to evaluate the safety and efficacy of Telitacicept in adult patients with early stage of SLE .

This is a phase 4, multicentre, randomised, double-blind, open-labeled study to evaluate the efficacy and safety of telitacicept in adult subjects with active early stage of SLE (disease duration less than 2 years).

Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of SLE according to the 1997 American College of Rheumatology (ACR) classification criteria or 2019 EULAR/ACR classification criteria
* 18-65 years of age
* body weight 45-90kg
* antinuclear antibody titers ≥1:80, and/ or anti-double-stranded DNA antibodies
* SLEDAI-2K score ≥8 scores
* Disease duration less than 2 years (defined as the duration between the first appearance of any symptom/sign attributed to SLE and baseline)
* A stantard therapy for at least 30d for patients who are not treatment-naive
* Negative pregnancy test for child-bearing women at screening and baseline
* Provide written informed consent

Exclusion Criteria:

* Known to be allergic to Prednisone Acetate, Meprednisone, Hydroxychloroquine, and Immunosuppressants including Mycophenolate Mofetil, Cyclophosphamide,et al
* Active serious neuropsychiatric systemic lupus erythematosus or other severe situations of SLE who need pulse steroid treatment
* severe lupus nephritis: 24hUP more than 6g, serum creatinine \> 221umol/L
* History of severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis) requiring intervention within 60 days of baseline (Day 1)
* Abnormal liver function (ALT or AST is 2 times higher than normal)
* Baseline IgG below the lower limit of the normal range
* Pregnancy or breastfeeding women
* Have a history of malignant tumors
* Have any serious acute, chronic or recurrent infectious disease (such as pneumonia or active stage of pyelitis, recurrent pneumonia, chronic bronchiectasis and tuberculosis)
* Chronic infections, such as Hepatitis B virus or hepatitis B and C and HIV
* Cardiac insufficiency with metabolic imbalance or severe high blood pressure (systolic pressure \> 160mmHg or diastolic pressure \> 100mmHg) or diabetics
* Active hemorrhage or peptic ulcer
* With other concommitant autoimmune disease;
* Receipt of B-cell-targeted therapy (including belimumab) within 1 year before randomization
* Receipt of IVIG within 28 days before randomization
* Receipt of TNF inhibitor, IL-1R inhibitor or plasma exchange therapy within 90 days before randomization
* Participated in other drugs clinical trials within 4 weeks.
* Receipt of live vaccine within 4 weeks before randomization
* Receipt of COVID-19 vaccine within 4 weeks before randomization
* Subjects who in the opinion of the investigator are not suitable to participate
Preemie Tots: A Pilot Study to Understand the Effects of Prematurity in Toddlerhood

The purpose of this study is to examine whether supplementation with certain polyunsaturated fatty acids can help development and behavior of children born preterm.


Eligibility Criteria:
Inclusion Criteria:

1. Child born at less than or equal to 29 completed weeks' gestation;
2. Child between 18 months, 0 days and 38 months, 30 days old chronological age;
3. Child admitted to NICU and/or had a Neonatology Clinic follow up visit scheduled.
4. Child showing some autistic symptoms;
5. Child between the 5th and 95th percentiles (per WHO growth chart) for weight at his/her most recent hospital visit;
6. English spoken in the home, demonstrate ability to communicate in English well-enough to understand study, informed consent, and study questionnaires; and
7. Have informed consent on file.

Exclusion Criteria:

1. Consume LCPUFA supplement drops, chews, powders, Pediasure, or fatty fish more than 2x per week;
2. Unable to tolerate venipuncture;
3. Any major malformation that would preclude participation;
4. Cerebral Palsy (quadriparesis only);
5. Deafness;
6. Blindness;
7. Bleeding disorder;
8. Type I diabetes;
9. Fragile X Syndrome, Rett Syndrome, Angelman Syndrome, Tuberous Sclerosis;
10. Non febrile seizure in the last month without a clear and resolved etiology;
11. Feeding problem that may inhibit full participation;
12. Known fish allergy;
13. Known canola/rapeseed allergy or sensitivity; or
14. Recorded score of \<70 on Bayley Cognitive Section within the past year.
Concordance Between Sonography Amd MRI for Presurgical Diagnosis of Uterine Mesenchymal Malignant Tumors

Determine the concordance between gynaecological sonography and pelvic MRI for the pre-surgical diagnosis of uterine malignant tumors.

The hypothesis that will be evaluated with this study is the concordance between the sonographic assessment following the terms and definitions to describe uterine pathology proposed by Morphological Uterus Sonographic Assessment (MUSA) and the pelvic MRI for the pre-surgical diagnosis of malignant mesenchymal uterine tumors in patients affected of symptomatic leiomyomas with clinical or sonographic risk factors for atypical fibroids.

If both explorations have the same efficiency for the diagnosis, one of those should be avoided, diminishing the costs and surgery delay for these patients.

Those women with uterine leiomyoma who present \>2 risk factors for uterine malignant mesenchymal tumors OR with sonographic criteria for atypical leiomyoma will be invited to participate in the study and will sign the informed consent.

After this first visit, the patient will undergo a gynecological sonography, serum lactate dehydrogenase (LDH) determination and a pelvic MRI, as it is done in our regular clinical practice.

All explorations will be performed in the same study center and will be done by independent physicians.

Then patients included will be addressed to a second visit to explain the results and surgery planning if it's needed.

One month after the surgery, one last visit will be conducted to perform a post-surgery control and give the final anatomo-pathological report of the surgery specimen. All data will be entered in the database for further analysis.

Eligibility Criteria:
Inclusion Criteria:

* \>18 years old
* Accept to participate in the study
* uterine leiomyomas who have \>2 risk factors for mesenchymal uterine malignant tumor OR sonographic suspicion of atypical leiomyoma.

Exclusion Criteria:

* \< 18 years
* Not being capable of understanding the study design
Feasibility and Reliability of Multimodal Evoked Potentials

Multimodal Evoked potentials (mmEP) reflect disease course of multiple sclerosis (MS) and are potentially suited as a biomarker for disease progression.

The acquisition of evoked potentials (EP) in this observatory trial is to evaluate the feasibility and test-retest reliability of motor and somato-sensory EP (MEP and SSEP) in an international multicenter setting in healthy subjects and subjects with multiple sclerosis (MS).

Multimodal EP (mmEP) is being developed as a predictive biomarker to determine the clinical response to therapy. MEP and SSEP contributes significantly to the predictive value of mmEP. The variability of MEP and SSEP has limited its use in multicenter clinical trials. Recent technological advances and standardization of procedures has decreased the variability. The objective of this study is to evaluate the reliability of MEP and SSEP and feasibility of performing MEP and SSEP in an international, multicenter setting. Establishment of the reliability and feasibility of MEP and SSEP will allow for further development of this predictive biomarker in future clinical trials.

Eligibility Criteria:
Inclusion Criteria (Healthy controls):

* Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
* Have no significant health issues, ie neuropathy or other demyelinating disorder that can affect testing.

Inclusion Criteria (Patients with MS):

* Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations
* Diagnosis of MS (all types) with an expanded disability status scale (EDSS) 0.0 to 6.5
* Have measurable responses on both MEP and SSEP in at least one upper and one lower limb on visit 2. The MEP and SSEP responses do not need to be in the same limb
* Have no comorbid condition (ie neuropathy) that could affect testing

Exclusion Criteria:

* Inability to comply with study requirements
* Unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment
* Any diseases (e.g., non-MS demyelinating diseases), with the exception of diagnosis MS for the MS Cohort, that in the opinion of the Investigator, could influence evoked potential results (including but not limited to medullary trauma, morbid obesity, limb amputation, diabetes, other polyneuropathy)
* Conditions interfering with magnetic stimulation (including but not limited to epilepsy, movable metal implants in the body such as pacemakers or stents)
* MS relapse within 3 months of either sessions
* Initiation of treatment or dose adjustment within 1 month of either sessions with 4-Aminopyridin, Carbamazepine, Baclofen, Tizianid
* Febrile illness within 3 days of either sessions.
Perioperative Immune Function and Clinical Complications in Pancreaduodenectomy

Perioperative immunologic signatures can predict the risk of postoperative complications.

The results will be puplished as two smanuscripts. The manuscript will focus on preoperative immunologisk data,the second manuscript will include both pre- and postoperative data.

OBJECTIVE Establish evidence for perioperative immunologic risk stratification of patient's risk for clinically postoperative inflammatory complications as a basis for future mechanism-based intervention studies.

Combining detailed immune assessment from cell-receptors to cell expression, cytokines, and complications with a temporal aspect is innovative and provides highly warranted novel multidimensional immunological insight.

METHODS Adult patients scheduled for PD on the suspicion of pancreatic cancer excluding patients receiving immunomodulating treatment 1 month properatively and/or autoimmune diseases. Patients scheduled for simultaneous procedures on major blood vessels, and/or adjacent organs (spleen, liver) are also not included. Inoperable patients, for instance, due to carcinosis, circulatory/ventilatory instability hindering procedure completion and/or concomitant surgery on major blood vessels, spleen, or liver, are excluded post-inclusion and will not be part of the primary analysis. Patients eligible for inclusion will be identified before their appointment at the Gastrosurgical Dept., Rigshospitalet which is the largest DK and North-European center with about 200 PD/yr annually.

Primary outcome:

Persistent postoperative hypotension, defined as need for vassopressor infussion on the morning after surgery to maintain middle arterial bloodpressure \>65 mmHg

Eligibility Criteria:
Inclusion Criteria:

* Scheduled for PD on the suspicion of pancreatic cancer
* Patients able to follow standardised surgical procedure including TIVA anaesthesia with epidural

Exclusion Criteria:

* Bilirubin \>100 µmol/ltr
* Patients receiving immunomodulating treatment 1 month properatively and/or autoimmune diseases and patients non-cenacerous cystic lessions
* Patients scheduled for simultaneous procedures on major arterial blood vessels, and/or adjacent organs (spleen, liver)
* Inoperable patients, for instance, due to carcinosis, circulatory/ventilatory instability hindering procedure completion and/or concomitant surgery on major arterial blood vessels, spleen, or liver, are excluded post-inclusion and will not be part of the primary analysis
* ongoing treatment with glucocortocoid, anti-tnf-alpha etc.
* patients diagnosed with rheumatological diseases, IBD or chronic infection (eg. HIV)
Extension Study of IONIS-GHR-LRx Administered to Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

The purpose of this study is to assess the safety and efficacy of extended dosing with IONIS GHR-LRx in participants with acromegaly as add-on to somatostatin receptor ligands (SRL) therapy.

This extension study will include participants up to 60 participants with acromegaly from Study NCT03548415. All participants will remain on the same dose from the previous study and receive IONIS GHR-LRx (SC) injection once every 28 days as add-on to SRL therapy for 53 weeks. At the end of 53 weeks, participants will enter a 14-week post-treatment (PT) evaluation period.

Eligibility Criteria:
Inclusion Criteria:

* Randomized in index trial (CS2) and completed the entire study, or completion of the treatment period for CS2 and completed or plan to complete PTWK5 visit with an acceptable safety profile, per investigator judgment
* Participants with confirmed stable monthly regimen of SRL for 3 months prior to screening
* Able and willing to participate in a 53-week treatment and 14-week post-treatment study

Exclusion Criteria:

* Treatment with any other acromegaly medications taken prior to Day 1 within the time period: bromocriptine: 2 weeks, carbergoline: 4 weeks, quinagolide: 4 weeks, pegvisomant: 4 weeks and pasireotide: 4 months
* Participant who received surgery for pituitary adenoma in the last 3 months prior to screening and participants needing and/or planning to receive surgery for the pituitary adenoma during the trial
* Unwilling to comply with required study procedures during the treatment and post-treatment periods
Microparticles Circulating Plasma Concentration in Atrial Fibrillation After Percutaneous Occluding of the Left Atrium

The aim of the study is to compare levels of differnts types of microparticles circulating before and after percutaneous occluding of the left atrium by patients with atrial fibrillation and patients control.

Hypothesis is that prothesis implantation will decrease levels of microparticles circulating in blood circulation because of occluding of the left atrium .


Eligibility Criteria:
Inclusion Criteria:

atrial fibrillation group:

* high embolic risk (CHADS-VASC2 score ≥4)
* formal and final contraindication to anticoagulant therapy
* no heart thrombus on ETO and TDM before percuraneous occluding

control group:

* suspicion of stable coronary artery disease, coronary angiography scheduled and double platelet aggregation (clopidogrel and aspirine)

Exclusion Criteria: for both groups

* congestive heart failure, severe aortic stenosis, EP or TVP early.
The Effect of Rigid Taping in Chronic Stroke Patients With Knee Hyperextension

In this study, it is aimed to examine the effect of rigid taping on hyperextension control in stroke patients with knee hyperextension in the stance phase of gait.

Hypothesis Ho: Rigid taping has no effect on the control of knee hyperextension in stroke patients.

H1: Rigid taping has an effect on the control of knee hyperextension in stroke patients.


Eligibility Criteria:
Inclusion Criteria:

* Having had a stroke at least 6 months ago
* Ambulation with or without a walking aid (walker, cane or tripod)
* To be between 0-3 points according to the Modified Rankin Scoring
* Presence of spasticity in any of the lower extremity muscles with a value of at least 1 according to the Modified Ashworth Scale
* Getting a score of 24 or higher on the Mini Mental Test
* Presence of hyperextension in the stance phase of gait

Exclusion Criteria:

* Having more than one stroke history
* Being diagnosed with dementia
* Having a previous diagnosis of orthopedic, psychiatric or other neurological disease
* Having a situation that prevents communication
* History of surgery or joint contracture involving the lower extremities and gait
Role of ABUS as an Alternative to Breast MRI in Assessing Response to Neoadjuvant Chemotherapy

Some women who have been diagnosed with a breast cancer will require chemotherapy as part of their treatment. The chemotherapy can be given before breast surgery - neoadjuvant chemotherapy or after breast surgery - adjuvant chemotherapy. Whether chemotherapy is given before or after does not affect the clinical outcomes for the woman - ie there is no disadvantage to the woman. Due to the fact that giving chemotherapy before has no disadvantages, many of the oncologists like to give the chemotherapy before because they can see if the breast cancer is responding. They are able to do this by using imaging. The best imaging test is breast MRI. Ultrasound can be used but studies have shown that it is not as good. However, whole breast ultrasound (ABUS) provides 3 dimensional information similar to breast MRI and the purpose of our study is to see if ABUS performs similar to breast MRI in being able to see if a tumour is responding to the chemotherapy. The breast MRI requires women to lie facing down and takes about 20mins. It involves an injection of contrast called gadolinium via a cannula. ABUS involves scanning the whole breast with the patient lying on their back and takes 10mins. There is no injection of contrast. MRI is an expensive test and often there is limited access to the scanner and so patients may have to wait for an appointment. ABUS because it is an automated process for obtaining the images can be performed in the breast unit in a timely manner without the issue of competing demands. All women who agree to take part in the study will have both the breast MRI - standard or care and the ABUS.


Eligibility Criteria:
Inclusion Criteria:

1. All female participants eligible for neoadjuvant chemotherapy and planning surgical treatment
2. Able to give informed consent

Exclusion Criteria:

1. All female particpants having neoadjuvant chemotherapy as palliative treatment with no surgery planned
2. Unable to provide informed consent
3. Unable to have breast MRI scan due to clautrophobia or allergy to gadolineum
The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

Determination of the effects of sildenafil citrate and epoprostenol when used in combination in patients with pulmonary arterial hypertension


Eligibility Criteria:
Inclusion Criteria:

* Patients with pulmonary arterial hypertension caused by primary PAH, associated with connective tissue disease or following surgical repair of a congenital heart lesion

Exclusion Criteria:

* PH other than PAH