cyrilzakka/clinical-trials huggingface dataset:
Gene Therapy for Metachromatic Leukodystrophy (MLD)

This Phase I/II clinical trial consists of the application of lentiviral vector-based gene therapy to patients affected by Metachromatic Leukodystrophy (MLD), a rare inherited Lysosomal Storage Disorder (LSD) resulting from mutations in the gene encoding the Arylsulfatase A (ARSA) enzyme. The medicinal product consists of autologous CD34+ hematopoietic stem/progenitor cells in which a functional ARSA cDNA is introduced by means of 3rd generation VSV-G pseudotyped lentiviral vectors.


Eligibility Criteria:
Inclusion Criteria:

* Pre-symptomatic MLD patients with the late infantile variant;
* Pre- or early-symptomatic MLD patients with the early juvenile variant;
* Patients for whom parental/guardian signed informed consent has been obtained.

Exclusion Criteria:

* HIV RNA and/or HCV RNA and/or HBV DNA positive patients;
* Patients affected by neoplastic diseases;
* Patients with cytogenetic alterations typical of MDS/AML;
* Patients with end-organ functions or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
* Patients enrolled in other trials/other therapeutic approaches that might become available;
* Patient who underwent allogeneic hematopoietic stem cell transplantation in the previous six months;
* Patient who underwent allogenic hematopoietic stem cell transplantation with evidence of residual cells of donor origin.
Non-Invasive Portal and Hepatic Vein Pressure Estimation

Background Portal hypertension (PH) is a spectrum of complications of end-stage liver disease (ESLD) and cirrhosis, with severe manifestations including ascites and gastroesophageal varices. It is therefore important that timely and easily diagnosing PH has relevant prognostic and therapeutic implications. The current gold standard to evaluate PH is by hepatic vein catheterization using the transjugular approach, and measuring the hepatic venous pressure gradients (HVPG).

Time-resolved, three-dimensional, three-directional velocity-encoded MRI, also termed four-dimensional (4D) flow MRI, has been shown superior accuracy over conventional two-dimensional (2D) phase-contrast MRI, in particular for quantification of regurgitant volumes and severity of cardiac shunts. Recently, the investigators developed new imaging methods based on 4D flow MRI for visualization of the vasculature of the abdominal blood flow circulation including the portal vein. Using the newly developed computation fluid dynamics (CFD) model the investigators could determine the absolute local blood pressure in the portal vein. Preliminary data in healthy volunteers seem promising, however, data in patients with ESLD including the correlation with invasively measured HVPG are lacking.

Objectives The primary objective is to develop and validate noninvasive CFD and 4D Flow MRI based HVPG calculation to estimate portal pressure in patients with end-stage liver disease (ESLD).

Methods In 50 adult patients with ESLD, submitted for liver transplantation (LT) screening, HVPG measurements using the transjugular approach according to the standard LT screening protocol, will be extended by 4D flow MRI measurements.

Anticipated results In patients with ESLD, portal pressure can be measured by 4D flow MRI and will replace the invasive transjugular approach. The measurements can be directly incorporated in the LT screening. Moreover, the possibility to easily measure portal pressure will be relevant for all patients with ESLD at risk for PH.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Patients will undergo a single non-invasive MRI-examination of one hour long after a four hour period of fasting. The risks associated with non-invasive MRI examinations is neglectable.


Eligibility Criteria:
Inclusion Criteria:

* Eligible for liver transplantation (LT) screening (which excludes pregnancy).
* Age ≥ 18 years and ≤ 75 (since \>75 is a contraindication for LT).
* Written informed consent.

Exclusion Criteria:

* Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc.).
* A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study.
Autism, Emotional Processing, and the Amygdala

Empathy imbalance hypothesis suggests that individuals with autism Spectrum Disorder (ASD) should have a deficit of cognitive empathy and a surfeit of emotional empathy. Considering that inconsistent amygdala reactivity to emotional faces might be ascribed to aberrant attention in ASD, the investigators hypothesized to investigate if there would be an imbalance between conscious and nonconscious emotional processing. This fMRI study recruited 26 youths and young adults with autism spectrum disorder and 25 matched controls, and measured their amygdala reactivity and functional connectivity in response to conscious and nonconscious (backward masked) perception of threatening faces.

Keywords: Autism Spectrum Disorder; amygdala reactivity; emotional processing; fMRI


Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of severity of Autism-Spectrum Disorders
* IQ \> 75

Exclusion Criteria:

* Neurological abnormalities,
* A history of epilepsy or seizures, head trauma a
* IQ \<75
A Study of AK112 in Patients With Unresectable Hepatocellular Carcinoma (HCC)

Phase II open label, multicenter study to evaluate the efficacy and safety of AK112 (PD-1/VEGF Bispecific) in patients with unresectable hepatocellular carcinoma (HCC).


Eligibility Criteria:
Inclusion Criteria:

* Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
* 18 to 75 years old.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Have a life expectancy of at least 3 months.
* BCLC stage B or C, not amenable to curative surgery.
* Hepatocellular carcinoma confirmed by histology/cytology. Cirrhosis meets the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Diagnosis of Liver Diseases (AASLD).
* At least one measurable untreated lesion.
* Child-Pugh class A.
* Has adequate organ function.
* All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

* With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues.
* History of malignancy other than HCC within 5 years, except that basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
* Have a history of hepatic encephalopathy or have a history of liver transplantation.
* With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion.
* Central nervous system (CNS) metastasis or meningeal metastasis.
* Prior immunotherapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
* Prior systemic bevacizumab and its analogues treatment.
* Severe bleeding tendency or coagulation dysfunction; occurred arteriovenous thromboembolic events or bleeding events due to esophageal and/or gastric varices within 6 months before the first administration.
* Known presence or history of required hormone treatment interstitial lung disease or non-infectious pneumonitis.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has undergone major surgery within 30 days prior to the first dose of study treatment.
* History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
Evaluation in Individuals with COPD and Asymptomatic Individuals

The literature does not provide sufficient information on the evaluation of frailty, handgrip strength, physical activity, kinesiophobia, and fatigue in elderly individuals with Chronic Obstructive Pulmonary Disease and asymptomatic elderly individuals. Additionally, there is a gap in the literature regarding the impact of COPD on these parameters in geriatric individuals diagnosed with Chronic Obstructive Pulmonary Disease . To fill this gap in the literature and to establish treatment approaches based on the results of parameters studied in elderly individuals with Chronic Obstructive Pulmonary Disease in future studies.

Chronic Obstructive Pulmonary Disease (COPD) is a prevalent condition among the elderly population, considered a leading cause of morbidity and mortality. It is characterized by chronic inflammatory responses associated with harmful particles or gases in the airways and lungs, resulting in persistent airflow limitation that is both preventable and treatable . While cough and sputum are reported as clinical symptoms in COPD cases, the most prominent clinical symptom is dyspnea. Age-related physiological changes and frailty lead to a decrease in levels of physical activity. The resulting deconditioning from reduced physical activity causes a decline in ventilation quality, creating a vicious cycle that progressively exacerbates dyspnea. This study involves the comparison of individuals diagnosed with COPD with asymptomatic geriatric individuals. Its aim is to examine the effects of COPD on frailty, handgrip strength, physical activity, kinesiophobia, and fatigue.

Eligibility Criteria:
Inclusion Criteria:

* Inclusion Criteria for COPD Patients:

  * Having received a diagnosis of COPD
  * Being 65 years of age or older
  * Volunteering to participate in the study
  * Not having any mental or communication issues that would hinder the completion of the questionnaires to be used in the research
* Inclusion Criteria for Asymptomatic Individuals:

  * Not having received a diagnosis of COPD
  * Being 65 years of age or older
  * Volunteering to participate in the study
  * Not having any mental or communication issues that would hinder the completion of the questionnaires to be used in the research

Exclusion Criteria:

* Exclusion Criteria for COPD and Asymptomatic Individuals:

  * Having a diagnosis of both physical and mental illnesses
  * Being diagnosed with unstable COPD
  * Having conditions such as unstable angina, prior heart attack, uncontrolled hypertension, cancer, and neurological disorders accompanied by functional limitations
  * Currently being addicted to alcohol or substances
  * Having severe visual and hearing impairments
  * Having undergone major surgery in the past few months
  * Having a history of recurring significant clinical infections.
A Predictive Model Based on Narrow Band Imaging for Early Gastric Cancerous Lesions

Without high diagnostic efficacy of endoscopic forceps biopsy (EFB) and with low diagnostic efficacy of narrow band imaging (NBI) in novice endoscopists and endoscopists of community hospitals in China, it is urgent to improve diagnostic efficacy for gastric cancerous lesions.The investigators will conduct a study to develop and validate a diagnostic model based on NBI for early gastric cancerous lesions under endoscopic observation.

Endoscopic forceps biopsy (EFB) is considered the gold standard and most commonly used for histological diagnosis of gastric epithelial neoplasia before proper management.Many studies have shown that there exist considerable discrepancies between EFB and subsequently resected specimens with discrepancy rate of 27.1-44.5%. On the other hand, with low diagnostic efficacy of narrow band imaging (NBI) in novice endoscopists and endoscopists of community hospitals in China, not higher diagnostic accuracy of gastric cancerous lesions could be observed. Here, the investigators will conduct a study to develop and validate a diagnostic model based on narrow band imaging for early gastric cancerous lesions under endoscopic observation, trying to improve overall diagnostic efficacy for gastric cancerous lesions.

Eligibility Criteria:
Inclusion Criteria:

* Suspected of having a cancerous lesions
* The age of patients is from 40-80 years
* Patients must undergo esophagogastroduodenoscopy

Exclusion Criteria:

* Clinical diagnosis of advanced gastric cancer
* Acute upper gastrointestinal bleeding
* Severe systemic diseases
* Refuse to attend the study
Focal Muscular Vibration in Patients with Severe Acquired Brain Injury

Severe acquired brain injury (sABI) is a group of disorders that cause long-term disability. Rehabilitation is essential to counteract bed immobilization, muscle failure, pain, and sensory deficits that can affect the clinical and rehabilitation pathway of these patients.

Focal muscle vibration (FMV) is a tool that uses low-amplitude, high-frequency vibrations that when applied to muscle-tendon units. This technique, administered at specific frequencies, amplitudes and durations, can generate action potentials of the same frequency as the stimulus applied to the muscle or tendon. This makes it possible to activate selected afferent fibers and stimulate targeted brain areas with persistent effects over time (long-term potentiation).

Regarding the effect of counteracting vibration spasticity, FMV is able to inhibit the reflex arc and induce reciprocal inhibition of functional agonist muscle. In addition, the strong proprioceptive stimulus generated by vibration is able to reach the primary motor and somatosensory cortex, enhancing cortical mechanisms that regulate co-contraction between agonist and antagonist muscles, thereby reducing muscle tone and joint stiffness. In many studies, this technique has been shown to be effective in reducing pain and joint stiffness by improving muscle contraction and motor control.

The present study aims to analyze the effects of focal muscle vibration in patients with sABI. This study is innovative for the setting, as it will take place for the first time within a neurorehabilitation hospital ward, for the intensity of the treatment as patients will undergo daily treatment sessions, for longer periods than protocols so far in the scientific literature. Finally, the cortical effects of the vibratory stimulus will be analyzed through the analysis of cortical neurophysiological correlates

Eligibility Criteria:
Inclusion Criteria:

* Age between 18-75 years
* Picture of subacute sABI (20 days to 6 months after the acute event), of any etiology (traumatic, vascular, metabolic)
* Presence of spasticity in the affected limb as assessed by the Modified Ashwort Scale (MAS) ≥ 1+

Exclusion Criteria:

* recent treatment with botulinum toxin (within 3 months);
* ongoing treatment with systemic muscle relaxant drugs (baclofen, tizanidine, benzodiazepines);
* deep vein thrombosis;
* central/peripheral accesses ipsilateral to the limb(s) to be treated;
* oncological diseases;
* epilepsy;
* open skin lesions or local infections.
Bioavailability of BI 10773 and Pioglitazone in Healthy Male Volunteers

The objective of the study was to investigate whether there is a drug-drug interaction between BI 10773 and pioglitazone when co-administered as multiple oral doses. Therefore, the relative bioavailabilities of BI 10773 and pioglitazone were determined when both drugs were given in combination compared with BI 10773 and pioglitazone given alone.


Eligibility Criteria:
Inclusion Criteria:

* Healthy males according to the following criteria:

  * Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG (electrocardiogram), clinical laboratory tests
* Age 18 to 50 years (incl.)
* BMI 18.5 to 29.9 kg/m2 (incl.)
* Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion Criteria:

* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
* History of relevant orthostatic hypotension, fainting spells or blackouts
* Chronic or relevant acute infections
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
* Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
* Participation in another trial with an investigational drug within two months prior to administration or during the trial
* Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 30 g/day)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration or during the trial)
* ALT (Alanine transaminase) outside the normal range or any other laboratory value outside the reference range that is of clinical relevance
* Inability to comply with dietary regimen of trial site
* Galactose or lactose intolerance, galactose or glucose malabsorption
Central Mechanisms of Chronic Pain and Fatigue Subtitle: Functional Imaging of Brain and Spinal Cord

Chronic pain and fatigue are characterized by peripheral and central mechanisms including low pain thresholds, temporal summation, peripheral and central sensitization. This application will focus on central factors of chronic pain and fatigue. Functional brain imaging will be used to characterized brain and spinal cord abnormalities that contribute to the mechanisms of these disorders.

Chronic fatigue (ME/CFS) and fibromyalgia syndrome (FM) are a chronic musculoskeletal pain disorder that predominantly afflicts women. Frequently associated insomnia, cognitive abnormalities, and fatigue may lead to early disability. No consistent soft tissue abnormalities have been identified so far in these patients. The cause of these disorders is unknown, no highly effective treatment is available and the current methods of diagnosis are imprecise and unreliable. The Investigators previously used quantitative sensory testing to improve upon diagnoses of these disorders by supplementing the current procedure of manipulating defined pressure points by hand and noting the presence or absence of pain. The quantitative methods of evaluation involve repetitive application of brief, non-injurious thermal/mechanical stimulation that normally produces a moderate degree of temporal summation of sensation intensity. The patients and normal control subjects will verbally rate the magnitude of late sensations elicited by each stimulus, using a numerical scale. Chronic pain in these patients results, at least partially, from exaggerated activation of central N-methyl-D-aspartate (NMDA) receptors as a result of enhanced input from unmyelinated peripheral afferent nerve fibers supplying deep tissues. Temporal summation of second pain can lead to central sensitization with subsequent signs of hyperalgesia and allodynia. Functional brain imaging of ME/CFS and FM patients, as proposed in this study, will be used to document their ratings of repetitive experimental stimuli and the resulting pain augmentation. Successful completion of this study will provide a new method for the evaluation of chronic pain/fatigue mechanism and their response to therapy.

Eligibility Criteria:
Inclusion Criteria:

* diagnosis of FM will require a history of chronic widespread pain as well as the presence of at least eleven out of eighteen paired tender points.
* diagnosis of ME/CFS will require a history of chronic fatigue persisting or relapsing for more than 6 months as well as the presence of at least four out of eight designated symptoms.
* willing to reduce anti-depressants to low levels like amitriptyline 10 mg/day, trazodone 50 mg/day, citalopram 20 mg/day, for at least five half-lives of the medication.

Exclusion Criteria:

* Patients unwilling or unable to discontinue or modify analgesics, hypnotics, anxiolytics, or anti-depressants during the study period will be excluded from this trial.
The Correlation Between AQP-4 Ab and the Visual Function of Patients With Demyelinating ON at Onset

To evaluate the optical coherence tomography (OCT), visual field (VF), Visual evoked po-tential(VEP) characteristics between neuromyelitis optica- related optic neuritis (NMOSD-ON) and multiple sclerosis- related ON (MS-ON) in a Chinese cohort.

Patients were sub-divided into an AQP4 seropositive group and an AQP4 seronegative group, according to the results of the AQP4-Ab test. All patients with complete medical histories underwent routine neurological examinations, brain MRIs, and ophthalmological examinations, including best corrected visual acuity (BCVA), intraocular pressure, slit lamp and fundus examination, VF and VEP, laboratory testing, including blood routine, HIV HBV HCV Syphilis, mitochondrial DNA sequencing, and a profile of autoantibodies, including antinuclear antibody (ANA), extractable nuclear antigen antibodies (SSA/SSB), rheumatoid factor (RF), anticardiolipin antibodies (ACA), and antithyroglobulin antibody.

Eligibility Criteria:
Inclusion Criteria:

* Optic neuritis patients

Exclusion Criteria:

* The presence of significant refractive errors (3D of spherical equivalent refraction or 2D of astigmatism), intraocular pressure of 21 mmHg or higher, systemic conditions that could affect the visual system, and a history of ocular trauma or concomitant ocular diseases, including a history of media opacification, ocular pathologies affecting the cornea, lens, retinal disease, glaucoma, or laser therapy. All patients in the study groups had an episode of ON more than six months before the study inclusion time point.
Open and Endoscopic Technique in Female Inguinal Hernia Repair. FemaleHernia

This randomized study compares open inguinal hernia repair (Lichtenstein hernioplasty) to endoscopic repair (TEP) in terms of chronic pain and recurrences in one and five years after operation.

The best operative technique in female inguinal hernia is not known. Some register studies recommend always laparoscopic hernia repair in females, but there are no randomized studies to show that laparoscopic repair is better than open hernioplasty. Our study compares operative complications, chronic pain and recurrences in Lichtenstein operation to totally endoscopic hernia repair (TEP) in 170 female patients with primary inguinal hernia. The patients are operated in six Finnish hospitals, randomized into 85 Lichtenstein vs 85 TEP and followed 1 week, 4 weeks, 12 months and 5 years. Main end-point in postoperative pain after one year, sencondary endpoints are sick leave, return to normal physical activity, complications of treatment, re-operations, chronic pain and costs of treatment.

Eligibility Criteria:
Inclusion Criteria:

* primary inguinal hernia in females

Exclusion Criteria:

* emergency operation
* recurrent hernia
* groin pain without hernia
* frail and sick patient ASA ≥ 4