cyrilzakka/clinical-trials huggingface dataset:
Ofatumumab in Portuguese Multiple Sclerosis Patients - an Observational Study

This non-interventional study will compare the effect of Ofatumumab treatment between patients that began Ofatumumab within the 3 years after Multiple Sclerosis diagnosis and patients that began Ofatumumab with more than 3 years of Multiple Sclerosis diagnosis in a real-world setting in Portugal.

This is a 2 cohort, multi-center, observational study carried out in Portugal that aims to describe the effectiveness of Ofatumumab in a setting of routine medical care. Primary data will be collected from Multiple Sclerosis patients who initiate Ofatumumab early and later in their disease (cohorts 1 and 2, respectively).

Data will be collected during 3 visits distributed over a maximum period of 24 months. Exceptionally, if the patient shows Expanded Disability Status Scale (EDSS) worsening in visit 2 or 3 (12 and 24 months after Ofatumumab initiation, respectively), there will be an additional visit 6±1 months after visit 2 or 3 for EDSS confirmation.

The study includes patients that have initiated Ofatumumab up to 12 months prior inclusion in the study OR Patients that are initiating Ofatumumab at the moment of study inclusion.

Patients in both cohorts will have to be treated with Ofatumumab for at least two years to compare No Evidence of Disease Activity (NEDA)-3 at 12 to 24 months, respectively.

Eligibility Criteria:
Inclusion Criteria:

To participate in the study, all the following inclusion criteria must be met:

* Patients aged 18 years or older
* Written informed consent obtained before participating in the study.
* Patient is willing and able to complete the assessments, including PRO questionnaires, as outlined in this study.
* Diagnosis of RMS per McDonald Criteria (2017) occurred prior to initiation of Ofatumumab.
* Treatment with Ofatumumab is in accordance with the Portuguese indication of Kesimpta® (i.e., treatment of adult patients with relapsing multiple sclerosis (RMS) with active disease defined by clinical or imaging features).
* Patients that have initiated Ofatumumab up to 12 M prior inclusion in the study OR Patients that are initiating Ofatumumab at the moment of study inclusion.

Exclusion Criteria:

To participate in the study, none of the following exclusion criteria must be met:

* Use of investigational drugs during the study, OR between Ofatumumab initiation and inclusion into the study, OR within 5 half-lives of investigational drug before Ofatumumab initiation, OR until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
* Use of high efficacy therapy (including Ocrelizumab, Natalizumab, Mitoxantrone, Rituximab and Alemtuzumab) in both cohorts prior to the initiation of Ofatumumab.
SB-773812 Administered In Adults With Schizophrenia

This is a two part study designed to evaluate the safety and efficacy of SB-773812 in the treatment of acute schizophrenia. Subjects with acute schizophrenia will be randomized in an adaptive design study to receive placebo, SB-773812 60mg or olanzapine 15mg for 12 weeks in Part A. An interim analysis will be conducted to assess the efficacy and safety of the SB-773812 60mg dose compared with placebo. Based on these data, up to two further doses of SB-773812 will be added to the randomization for Part B.


Eligibility Criteria:
Inclusion Criteria:

* Meets the diagnostic criteria for schizophrenia as defined in DSM-IV.
* PANSS total score of at least 70 at Screen and Baseline and a minimum score of 4 (moderate) on at least 2 of the following: conceptual disorganization (P2) hallucinatory behaviour (P3) suspiciousness (P6) or unusual thought content (G9) at the Screen and Baseline visits

Exclusion Criteria:

* Subjects with a history of epilepsy or other seizure disorder, first episode of schizophrenia or other psychotic disorders (e.g. residual type schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, etc.)
* Bipolar disorder, a history of substance dependence, or a medical or psychiatric disorder that would interfere with the accurate assessment of safety or efficacy are not eligible.
Effects of Weekly Dosing of D-cycloserine on Cognitive Function in Individuals With Schizophrenia

The study aims to assess the effects of single dose and repeated weekly dosing of 50mg d-cycloserine versus placebo on cognitive and memory functioning in schizophrenia patients. The study will also examine the effects of 50mg d-cycloserine on positive symptoms and negative symptoms, as well as assess tolerability and side-effects.

This is a ten-week, parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 2, 3. 4, 5, 6, 7, 8 \& 10 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in 60 adult outpatients with schizophrenia.

Specific aims:

1. Assess the effects of a single dose of D-cycloserine 50 mg on cognitive functioning compared to placebo.
2. Assess the effects of repeated weekly dosing of D-cycloserine on cognitive functioning at week 8 compared to placebo.
3. Assess the effects of repeated weekly dosing of D-cycloserine on memory functioning once a week 1 hour after medication administration compared to placebo.
4. Assess the persistence of learned information in a no-treatment follow-up assessment at Week 10 in the D-cycloserine group compared to the placebo group.
5. Assess effects of weekly D-cycloserine dosing on positive \& negative symptoms at week 8 compared to placebo.
6. Assess tolerability and side effects of weekly D-cycloserine compared to placebo.
7. Assess the effects of d-cycloserine dosed weekly for seven weeks on reward responsiveness as measured with the response bias task compared with placebo.
8. Assess the effects of d-cycloserine dosed weekly for seven weeks on measures of functioning.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female
2. Age 18-65 years
3. Diagnosis of schizophrenia or schizoaffective disorder, depressed type
4. Stable dose of antipsychotic for at least 4 weeks.
5. Able to provide informed consent
6. Able to complete a cognitive battery

Exclusion Criteria:

1. Current treatment with clozapine
2. Dementia
3. Seizure disorder
4. Unstable medical illness
5. Active substance abuse
6. Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
Initiative for Clinical Long-read Sequencing

The study aims to comprehensively introduce Long-read Genome sequencing (LR-GS) based genetic testing into clinical routine. In order to demonstrate the superiority of untargeted LR-GS over Short-read Genome sequencing (SR-GS) to establish firm genetic diagnoses, the investigators will rely on a multi-center "Translate Nationale Aktionsbündnis für Menschen mit Seltenen Erkrankungen" (Translate National Action Alliance for People with Rare Diseases Germany, TNAMSE) cohort of unsolved patients with neurological, neurodevelopmental, and imprinting disorders that is expectedly enriched for complex genomic variation. Within the framework of genomDE, the investigators will then implement, for the first time, LR-GS in the diagnostic work-up of a prospective cohort of patients with a broad range of clinical indications including rare diseases and cancer predisposition.

The proposed study aims to develop a blueprint for the implementation of LR-GS in clinical diagnostics. Hence Standard Operating Procedures (SOPs) and guidelines for library preparation, bioinformatic analysis, and clinical interpretation will be compiled. Furthermore, the investigators intend to develop an open source 'gold standard' bioinformatics pipeline, addressing all relevant types of genomic alterations, thus providing the bioinformatic basis for a streamlined implementation of LR-GS at other sites. In addition to in-depth phenotype information the availability of SR-GS will be instrumental to benchmark the ability to detect different types of genomic variation. Additional relevant issues for genetic testing such as variant calling in difficult-to-map genomic regions, detection of genomic methylation patterns, characterization of repeat expansion and duplicated genes, and haplotype-phased genome de novo assembly will be addressed. Moreover, based on the strong background in Artificial Intelligence (AI) driven variant prioritization in the consortium, the investigators aim to implement and/or develop tools that enable an efficient prioritization of disease-causing variants. Beyond the usage within the context of the proposed study, generated datasets will be made available according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles for national (German Human Genome-Phenome Archive, GHGA) and international (European Genome-Phenome Archive, EGA, Genome-Phenome Analysis Platform, GPaP) data repositories. the investigators aim to establish a population scale reference dataset for Structural variants (SV), which is absolutely mandatory in the context of rare disease diagnostics.

Eligibility Criteria:
Inclusion Criteria:

* Unclear molecular cause of the disease (retrospective cohort)
* Indication for genome diagnostics (prospective cohort; e.g. within the initiative for genomic medicine (genomDE) based on §64e SGB V)
* Suspected genetic cause of the disease

Exclusion Criteria:

- Missing informed consent of the patient or legal guardian
Robotic Pharmacological Anesthesia System for Elective Cardiac Surgery

Closed loop systems for anaesthesia have been shown to be more efficient than manual administration and than Target Control Infusion systems (TCI). So far, there is only one single-center study demonstrating that a system using simultaneously three closed loops for each component of anaesthesia (hypnosis, analgesia and muscle relaxation) is possible, safe and is more efficient than manual administration of anaesthetic drugs. Although the results of this study are very encouraging, they are limited by its sample of patients recruited for non-cardiac surgery only.

The hypothesis of the present trial is that cardiac anesthesia using a completely automated anesthesia delivery system, encompassing each components of anesthesia (hypnosis, analgesia and muscle relaxation) is feasible, safe and reliable.

Thus, the objective of the present trial is to test this pharmacologic anesthesia robot on patients scheduled for elective cardiac surgical procedures with extracorporeal circulation.

Hypnosis is monitored during the surgery according to the brain activity values provided by an objective monitoring parameter, called Bispectral Index (BIS).

A BIS target of 45 is aimed trough the surgery. Performance of propofol hypnosis will be determined clinically by recording the % of sedation time during which the actual BIS is within 10% of the target BIS (excellent control), within 11 -20% (good control), between 21-30% (fair control) and beyond 30% of target (inadequate control).


Eligibility Criteria:
Inclusion Criteria:

* Elective patients
* Patients scheduled to receive an extracorporeal circulation
* Patients aged 18 and older

Exclusion Criteria:

* Minor
* Unable to provide informed consent
* Comatose patients
* Patients with dementia
* Patient who underwent neurosurgery
* Pregnant women
* Patient with muscle disease
* Allergy to Propofol and/or remifentanil
In Vitro Detection of Tissue Abnormality

Intraoperative ex-vivo use of the ClearEdge Imaging Device in Breast Conserving Surgery to image the excised tissue surgical margins. The study is designed to demonstrate reduction in the need for repeat surgeries after breast conserving surgeries by using the ClearEdge as an adjunct imaging device to the standard of care.

Intraoperative real-time margin assessment of breast conserving surgeries can reduce the need for repeat operations due to cancer involved margins. Repeat operations result in excessive removal of benign tissue, increased risk for infection, slower healing and inferior cosmetic results. In the current standard of care, the status of the margins is determined by pathology only several days after surgery. An intraoperative assessment of the margins enables complete tumor excision in a single surgery.

The proposed randomized controlled study will evaluate the benefits of adding the ClearEdge imaging device to the Standard of Care (SoC) of margins assessment in breast conserving surgeries. The study will assess whether there is an improvement in the detection of cancer involved margins by measuring whether removal at the time of primary surgical treatment can reduce the need for repeat surgeries as compared to the SoC, which does not use the device.

ClearEdge is a CE marked device already been used in several hospitals in the UK. It was used in a prospective single arm and 2 phases clinical study. It was demonstrated that surgeons successfully used the device to identify cancer involved margins and that it can reduce the need for repeat surgeries by meeting the margins depth criteria to require repeat operations. European Journal of Oncology Surgery. 2016; 42 (12): 1834-1840. In addition, the device was clinically evaluated by several hospitals.

Eligibility Criteria:
Inclusion Criteria:

* Patients aged 25-80 who are scheduled for surgical excision of tissue.

Exclusion Criteria:

* No prior history of surgery at location of current surgery.
Association of Platelet Parameters With Bleeding Severity in Children With ITP

Patients with severe immune thrombocytopenia (ITP) present with similarly low platelet counts but varying bleeding symptoms, making it difficult to predict the disease course and to decide on an appropriate treatment plan. In a single-center study, platelet parameters including the immature platelet fraction, the absolute immature platelet count , and functional response markers were found to be significantly associated with patient bleeding severity, independent of platelet count. This study aims to confirm and replicate these findings in a multi-center patient population and to investigate the use of these parameters to better predict disease severity and bleeding events.

Many children with severe immune thrombocytopenia (ITP) present with mild symptoms and their disease spontaneously resolves within 3 to 6 months. However, a subset of pediatric ITP patients experience severe bleeds and their symptoms persist for more than 6 to 12 months. Both patient populations present with similarly low platelet counts, making it difficult to predict the disease course and to decide on a treatment plan. The current American Society of Hematology treatment guidelines advise that most cases of ITP may be managed through close observation, while pharmacological interventions that may result in treatment-related toxicities may be used in patients with more severe bleeding symptoms. In order to improve the care and management of pediatric patients with ITP, it is necessary to develop a better predictor of bleeding events and disease severity than the patient's platelet count.

In a previous single-center study, investigators studied the association of different platelet parameters with patient bleeding severity. Using whole blood from patients diagnosed with severe ITP, investigators measured the immature platelet fraction (IPF) and absolute immature platelet count (IPC) through a hematology analyzer (Sysmex XN-1000). Investigators performed functional tests on the platelets and analyzed them through flow cytometry. In this study, the investigators found that the IPF and IPC is associated with patient bleeding severity, independent of platelet count. It was also determined that functional activation markers such as P-selectin and glycoprotein (GP) IIb-IIIa are significantly associated with subsequent bleeding severity in children, independent of platelet count. The results of these proposed studies in ITP patients may suggest clinically relevant uses of these assays.

To confirm these findings, this trial will repeat the previous study in a multi-center patient population, including a greater number of patients with severe bleeding and low platelet counts.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosed with primary or secondary immune thrombocytopenia.
* Platelet count of \< 50 x 10\^9/L

Exclusion Criteria:

* May not have received aspirin 10 days prior to study entry.
* May not have received nonsteroidal anti-inflammatory drugs (NSAIDs) 3 days prior to study entry.
PET/CT Imaging for Radiation Dosimetry, Plasma Pharmacokinetics, Biodistribution, Safety and Tolerability and Diagnostic Performance of BAY86-7548 in Patients With Prostate Cancer and Healthy Volunteers

Visual assessment of diagnostic PET/CT (positron emission tomography/computed tomography) images obtained after a single intravenous injection of BAY86-7548 in patients with cancer.


Eligibility Criteria:
Inclusion Criteria:

* Healthy volunteers:

  * males, \>/=50 and \</= 65 years of age
* Cancer patients:

  * males \>/= 45 years of age
  * Patients had an MRI of the prostate and/or a positive choline or acetate PET/CT for diagnosis (Note: MRI, choline and acetate PET/CT are optional for primary prostate cancer patients) of recurrence prostate cancer and the primary cancer disease is/ will be histologically confirmed.
  * The prostate cancer is histologically confirmed and results of histology are available.
  * Patients with primary prostate cancer: \>/= 20 percent of biopsy material should be affected by cancer in the histopathological evaluation.
  * Patients with primary prostate cancer: Patient is scheduled to undergo prostatectomy.

Exclusion Criteria:

* Concurrent severe and/or uncontrolled and/or unstable other medical disease (e.g. poorly controlled diabetes, congestive heart failure, myocardial infarction within 12 months prior to planned injection of BAY86-7548, unstable and uncontrolled hypertension, chronic renal or hepatic disease, severe pulmonary disease) which could compromise participation in the study
* Known sensitivity to the study drug or components of the preparation.
Biomarker(s) for Glucocorticoids

The investigators have shown that patients with adrenal insufficiency (Addison's disease), a rare disorder, have doubled the expected mortality rate in Sweden despite Standard of Care glucocorticoid (GC) replacement. One % of the Swedish population are, however, receiving GCs for inflammatory diseases, but management is empirical and adjusted to underlying disease activity. The desired anti-inflammatory therapeutic effects cannot be differentiated from the adverse metabolic (osteoporosis, obesity, diabetes mellitus) and immunosuppressive side effects of GC. This frequently results in suboptimal GC therapy with adverse effects due to over-dosing or poor efficacy due to under-dosing. The primary aim is to identify a biomarker for the metabolic effects of GCs. Patients with Addison's disease completely lack endogenous GCs and can therefore be considered a human GC knock-out model. They can therefore be studied during near-physiological exposure and during GC starvation. This will uniquely allow a very clean biomarker identification model (using transcriptomics, proteomics and metabolomics). The secondary aim is to validate candidate biomarker(s) in a dose-response study using the same patient population. A biomarker of GC actions will make it possible to individualised therapy during pharmacological GC treatment. It would allow GC replacement to be monitored in Addison's disease and could become a specific diagnostic tool in patients with GC deficiency and excess (Cushings syndrome).


Eligibility Criteria:
Inclusion Criteria:

* Primary adrenal insufficiency under stable glucocorticoid replacement therapy (15-30 mg of Hydrocortisone stable dose the last 3 months) due to autoimmune adrenalitis (disease diagnosed at least 12 months before inclusion), age 20-60 years, BMI 20-30 kg/m2, and ability to comply with the protocol procedures.

Exclusion Criteria:

* Glucocorticoid replacement therapy for indication other than primary adrenal treatment, any treatment with sex hormones inclusive contraceptive drugs, treatment with levothyroxine, diabetes mellitus, renal or liver failure, significant and symptomatic cardiovascular disease.
RA-2 13-cis Retinoic Acid (Isotretinoin)

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research work has suggested that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. We think that giving men with low sperm counts retinoic acid may increase their sperm counts and improve their chances of fathering a pregnancy. We want to see if retinoic acid administration over twenty weeks can increase sperm production and help infertile men become fathers without the need for In vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). We also want to see if adding calcitriol with retinoic acid will improve sperm motility in a sub-set of subjects.

This is a 20 week, unblinded, two-arm pilot study to determine the impact of therapy with 13-cis retinoic acid and calcitriol on sperm indices in infertile men. Twenty infertile men, ages 21-60 with abnormal sperm analyses will be enrolled for 20-week and given 20 mg 13-cis retinoic acid, twice daily. Subjects#11-#20 will also be administered calcitriol to see if adding calcitriol with Accutane will improve sperm motility. All subjects will be closely followed for side effects related to treatment. The impact of treatment on indices of spermatogenesis will be determined by monthly seminal fluid analyses.

Eligibility Criteria:
Inclusion Criteria:

* Subjects will be infertile men (no pregnancy with partner with normal cycles and normal hysterosalpingogram despite \>1 year of unprotected intercourse).
* Abnormal sperm analyses with a total, motile sperm count of less than 10 million sperm as assessed by semen analysis on two occasions separated by one week.
* In the opinion of the investigator, is able to comply with the protocol, understand and sign an informed consent and HIPAA (Health Insurance Portability and Accountability Act ) form.

Exclusion Criteria:

* Men participating in another clinical trial
* Men not living in the catchment area of the clinic
* Clinically significant abnormal findings at screening
* Known genetic infertility (e.g. Klinefelter syndrome or Y-chromosome microdeletions),
* Hypogonadotropic hypogonadism (that might respond to gonadotropin injections),
* The use of anabolic steroids, illicit drugs, or the consumption of more than 4 alcoholic beverages daily
* Severe mental health problems requiring medications
* Current therapy with retinoic acid (e.g. Accutane) or vitamin A.
* Score of greater than 15 on the Patient health questionnaire (PHQ9).
* Abnormal serum chemistry values according to local laboratory normal values which indicate liver or kidney dysfunction. Other abnormal lab values may also be exclusionary, at the discretion of the investigator
* Men with a personal history of serious psychiatric disorders
* Men currently receiving tetracycline containing medications
* Men currently receiving phenytoin
* Men with a history of inflammatory bowel disease
* Men with a history of bone disease
* Men who have used isotretinoin within eight weeks of the start of dosing
* Men with elevated serum triglycerides