cyrilzakka/clinical-trials huggingface dataset:
Molecular and Cellular Mechanisms of Lysosomal Storage Diseases

The lysosome is a specialized part of the cell that functions to degrade metabolic wastes in the cell. Defects in the functioning of the lysosome result in accumulation and subsequent storage of such metabolic wastes. These defects lead to conditions known as lysosomal storage diseases (LSD). LSDs are caused by inherited genetic mutations and there are over 40 genetically distinct lysosomal storage diseases. Within each specific lysosomal storage disease there are variances in severity of disease, age of onset, and clinical presentation. Though the genetic mutations contributing to the disease have been largely clarified, the molecular and cellular mechanisms that contribute to variations in each distinct LSD remain unclear. With this study we intend to better understand at the cellular and molecular level how the accumulation and storage of metabolic wastes in the lysosome affect the clinical manifestation of LSDs, to detect changes in these mechanisms upon treatment administration, and to correlate these results to genetic information. The knowledge obtained from this research study could lead to better ways to diagnose and treat lysosomal storage diseases.


Eligibility Criteria:
Inclusion Criteria:

* Subject is greater than or equal to 1 day of age and less than or equal to 100 years of age
* Signed Informed Consent/Assent
* Subject is able and willing to comply with study protocol requirements.
* From clinical or blood laboratory findings subject has evidence of a lysosomal storage disease or a family member of a patient with lysosomal storage disease

Exclusion Criteria:

* Pregnant woman
Treating the Fear of Gaining Weight in Anorexia Nervosa

The main aim of this study is to develop a virtual reality (VR) embodiment-based exposure technique to improve the treatment of anorexia nervosa (AN). A systematic and hierarchical body exposure intervention in which the patient owns a virtual avatar is proposed. At first, the virtual body matches with the real measurements of the patient, then the experimenter will progressively increase Body Mass Index (BMI) values of the virtual body during the exposure sessions until a healthy BMI value is reached (e.g. BMI score of 20). In this study a VR embodiment-based technique that combines visuo-motor and a visuo-tactile stimulation procedures is proposed in order to increase illusory feelings of ownership over the virtual body. It is hypothesised that adding a VR-based body exposure intervention to the classical cognitive behavioral therapy (CBT) will significantly reduce symptomatology in AN patients.

In order to evaluate the efficacy of the addition of a VR body exposure component to the usual treatment, a randomized controlled clinical trial will be conducted. 54 patients with a primary diagnosis of anorexia nervosa and a BMI \> 18.5 will be randomly assigned to the experimental group receiving VR body exposure in addition to cognitive behavioral therapy or control group, which receives cognitive behavioral therapy only. Data regarding eating disorder symptomatology and body related attention will be collected before and at the end of the intervention, as well as after six months of follow-up. In the systematic and hierarchical VR body exposure intervention, which consists of 5 weekly exposure sessions, patients will gradually be exposed to increases in the BMI of their virtual avatar. Each session starts by inducing illusory feelings of ownership over the virtual body by the means of visuo-tactile and visuo-motor stimulation. Then patients are exposed to their virtual bodies in order to achieve the habituation or extinction of the anxiety response to their body image and, consequently, reduce the fear of gaining weight. During exposure, patients will be asked to focus on different parts of the virtual body, by asking what they think and feel about them. Body ownership illusion, body-related anxiety and fear of gaining weight will be assessed within each session by means of visual analogue scales.

Eligibility Criteria:
Inclusion Criteria:

* patients with primary diagnosis of anorexia nervosa (DSM-V)
* from the age of 14 years
* with BMI \<18.5

Exclusion Criteria:

* visual deficits
* epilepsy or neuroleptic medication
* psychotic disorder
* bipolar disorder
* medical complications
* pregnancy
* clinical cardiac arrhythmia
The Emergency Call on Drowning

This study aims to 1) describe patient-, setting-, and dispatcher-related characteristics in drowning-related emergency calls to the Emergency Medical Dispatch Centre (1-1-2 emergency phone) and 2) factors associated with 30-day survival. The investigators will separately analyse drowning-related out-of-hospital cardiac arrest (OHCA) and drowning-related non-OHCA. If feasible, the investigators will qualitatively analyse the calls to identify and describe potential barriers for an optimal handling strategy.

Previous studies have explored emergency priority levels, emergency call categorisations, barriers to assessing an emergency call, and the effects on the outcome. However, this has never been done specifically for drowning patients. Drowning presents a rare and special circumstance that may be particularly complex for laypeople and medical dispatchers for several reasons. Despite this complexity and medical dispatchers' potential to optimize treatment and improve outcomes in drowning incidents, the characteristics of drowning-related emergency calls have never been explored.

This protocol presents a registry-based cohort study of drowning-related emergency medical calls to the EMDC (1-1-2 emergency phone) with 30-day follow-up.

Data from the national Danish Prehospital Drowning Data will be linked with audio files and electronic data from the EMDC database using the patient's unique civil registration numbers.

The investigators will construct two lists of variables: one list for OHCA and one for non-OHCA emergency calls. Data collection from the EMDC database will consist of three phases.

In phase 1, three independent reviewers will listen to 20 emergency calls on drowning (10 OHCA and 10 non-OHCA) to identify relevant variables from the calls (e.g., presence of key symptoms \[since an emergency call often does not contain information regarding the absence of symptoms\], communication barriers \[anything that comes in the way of receiving and understanding information\], pre-arrival instructions to callers etc.).

In phase 2, the same reviewers will listen to 20 other emergency calls (10 OHCA and 10 non-OHCA) and use the lists for data collection to determine the data availability and completeness. This may result in modifications to the lists of variables. The investigators will use the results as a basis for reviewer training and calculate inter-rater reliability.

Once the reviewers' performances are satisfying (defined as Fleiss kappa ≥0.8), the investigators will move to phase 3 and collect data for all the drowning calls. Emergency calls will be stratified as OHCA or non-OHCA calls.

Eligibility Criteria:
Inclusion Criteria:

* Patients at all ages registered in the Danish Prehospital Drowning Data are eligible.

Exclusion Criteria:

* Obvious clinical signs of irreversible death (decapitation, decomposition, post-mortem lividity, post-mortem rigidity)
* A valid Do-Not-Attempt-Resuscitation (DNAR) order or other code status orders limiting life-sustaining therapies
* Missing or corrupted audio files
* Missing identification number
* Missing 30-day survival
Evaluating Innovative Technologies and Approaches to Addressing Cervical Cancer in Gaza and Maputo Cidade Provinces in Mozambique

The goal of this operational research study is to develop, implement and test integrated CCS\&PT and voluntary FP service delivery models to evaluate whether integrated service delivery can optimize uptake and health impact of both services. The study objectives and learning questions are listed below, along with key outcomes that will be measured.

Objectives:

The study objectives are outlined below:

1. To quantify the health impact of CCS\&PT on the uptake of voluntary FP services.
2. To quantify the health impact of voluntary FP on the uptake of CCS\&PT services.
3. To determine which promotional strategies are most effective to increase uptake of CCS\&PT services.
4. To identify cost to deliver high quality CCS\&PT services integrated into existing voluntary FP programs.
5. To determine client and provider acceptability of integrated CCS\&PT and voluntary FP services using new screen and treat technologies.

Eligibility Criteria:
Inclusion Criteria:

* Women 30 - 49 years or all women living with HIV
* Not currently pregnant
* Patients with a cervix (women who have undergone a total hysterectomy with removal of the cervix are not eligible)
* Living in Maputo or Gaza
* Willing and able to provide informed consent for services.

Exclusion Criteria:

* Not meeting the inclusion criteria
* Physical or mental impairment that inhibits participation in the study
* Pregnant women
Comparison of Mortality Impact of Coagulation Rotative Thromboelastometry Analysis Versus Standard Analysis

Digestive hemorrhage is a common cause of acute hemorrhage in France, and its mortality remains high despite improvement of endoscopy technique and therapeutics. Hemostasis disorders are an important issue in the patient care both in severity diagnostic and therapeutic plan.

Standard technique of coagulation analysis (prothrombin ratio, activated partial thromboplastin time, fibrinogen and platelet count) do not provide to guide practitioner in reanimation of hemostatic patients in particular when coagulation defect preexisting to the digestive hemorrhage.

In this respect, the main objective of this study is to evaluate the interest of rotative thromboelastometry in the care of patient with digestive hemorrhage and its mortality impact.

Eligibility Criteria:
Inclusion Criteria:

* Hospitalized patient in reanimation unit or continuous monitoring for digestive hemorrhage before or immediately after digestive endoscopy
* Digestive hemorrhage diagnostic: melena and/or rectal bleeding and/or hematemesis
* Affiliation to the social security
* Have signed an informed consent

Exclusion Criteria:

* Pregnant or nursing woman
* Without digestive fibroscopy
* With an anticoagulant treatment
* With a congenital coagulopathy
* Decision of therapeutic limitation or moribund patient
* With a digestive hemorrhage after an hospitalisation in reanimation unit for an other reason
* Participation in an other study in previous 30 days
* Under trusteeship, guardianship or judicial safeguards
Wedged Insoles for Management of Knee Osteoarthritis

Knee osteoarthritis (OA) is commonly treated using laterally wedged insoles. Although these insoles typically reduce knee abduction moments (KAM) - a variable associated with knee osteoarthritis - and thus are believed to be beneficial for OA management, recent research has indicated that in some cases lateral wedge insoles actually increase knee joint loads. In such cases, a medial wedge may be more appropriate.

The purpose of this study is to evaluate the influence of reduced KAMs on pain over 3-months for patients with knee OA. It is hypothesized that pain reduction will be directly related to KAM reduction.

Forty-six participants with knee OA will be recruited to participate. Each will undergo biomechanical gait analysis to determine the wedge type that most greatly reduces knee adduction moments. In addition, each participant will undergo a Dual Energy X-Ray Absorptiometry (DXA) scan to quantify adiposity. Finally, participants will complete a series of questionnaires to evaluate pain, function, physical activity, footwear comfort and injury history. Participants will be randomized into either a wait list control group (no insole) or experimental group (medial or lateral wedged insole), and monitored for 3 months.

Changes to pain, function, comfort and physical activity from baseline to 3 months will be assessed within the control and experimental groups. Regression analyses will be conducted on the experimental group to determine if a relationship exists between reduced KAMs and reduced pain over 3 months. Comparisons will also be made between the control and experimental groups.


Eligibility Criteria:
Inclusion Criteria:

* Physician-diagnosed knee osteoarthritis (using American College of Rheumatology clinical and radiographic criteria)
* Kellgren-Lawrence grade 1, 2, 3 or 4
* Primary symptoms and disease location must be attributed to medial tibiofemoral compartment
* KOOS pain of 75 points or lower (where 0 is worst pain and 100 is no pain)

Exclusion Criteria:

* X-ray older than 2 years
* Viscosupplementation within past 6 months
* Cortisone injection in past 3 months
* Narcotic pain medication within past 3 months
* Use of knee unloading brace interventions in past 2 months
* Recent (past 6 months) knee or neuromuscular injury that could bias pain assessments or gait analysis results
* No KAM reduction with either lateral or medial wedge insole
The Association Between Radiation Dermatitis and Skin Microbiome in Breast Cancer Patients

The breast cancer patients who received radiotherapy after mastectomy and breast reconstruction will be enrolled. The skin microbiome before radiotherapy and its changes after radiotherapy will be analyzed systematically to find out whether the skin microbiome is associated with the severity of radiation dermatitis.

Radiotherapy is an important treatment for breast cancer patients. About 95% of patients receiving radiotherapy will develop a degree of radiation dermatitis. Radiation dermatitis is usually limited to the site of radiation treatment. Symptoms vary and can range from itching, burning and pain to open or bleeding ulcers, which can greatly affect the quality of life of patients. Severe acute radiation dermatitis can lead to interruption or delay of treatment. At present, there is no standard for the prevention and treatment of radiation dermatitis. Our skin is home to millions of bacteria, fungi and viruses which compose the skin microbiota. Skin microbiota interacts with skin and affects physiology and immunity of the skin. Previous studies have reported the effects of radiotherapy on skin and immune system. However, so far, no studies have analyzed the effects of radiotherapy on skin microbiome and how skin microbiome affects the skin immune responses after radiotherapy. In this study, the breast cancer patients who received radiotherapy after mastectomy and breast reconstruction will be enrolled. The skin microbiome before radiotherapy and its changes after radiotherapy will be analyzed systematically to find out whether the skin microbiome is associated with the severity of radiation dermatitis. The long-term goal of this study is to deepen the understanding of the role of skin microbiome in the occurrence and development of radiation dermatitis, and provide a basis for subsequent exploration to reduce radiation dermatitis by regulating skin microecology.

Eligibility Criteria:
Inclusion Criteria:

1. Female patients
2. Invasive breast cancer confirmed by pathology
3. Underwent mastectomy and breast reconstruction
4. Radiotherapy after breast reconstruction
5. ECOG score 0-1
6. Signed informed consent

Exclusion Criteria:

1. Previous breast or chest radiotherapy
2. Other serious skin diseases (systemic lupus erythematosus, skin sclerosis, et al) and cannot receive radiotherapy
3. Pregnant women
4. Patients who are unwilling or unable to receive regular follow-up.
Effect of the Abutment-Prosthesis Connection on Marginal Bone Loss and Gingival Sealing Around Dental Implants

In dental implant restoration, available literature demonstrates the advantage of using tall abutments, with a change of diameter with respect to the implant and a conical internal connection in the abutment-implant gap. However, for multiple restorations, the abutment-prosthesis connection has not been studied in detail. The "multi-unit" systems, both standard and brand specific, have either a flat or butt joint or an cone. In any case, both are external connection systems. Recently, an internal-type abutment-prosthesis connection system has been developed. Although it is proving its usefulness in single restorations, its use in multiple restorations compared to traditional systems has not been studied.

Therefore, taking into account all of the above, the present study has the overall objective of analyzing marginal bone loss (MBL) and adaptation of soft tissues by comparing a multiple prosthesis system of the "external, flat" type versus an external system of the "internal, conical" type.


Eligibility Criteria:
Inclusion criteria:

* Kennedy class I or II (unilateral or bilateral free end) or III (posterior intermediate edentulous section) mandibular requiring 2 implants to restore at least 2 molars, 2 molars and 1 premolar, or 2 premolars and 1 molar.
* Possibility of placing a transgingival abutment at least 2 mm high.

Exclusion criteria:

* Need for simultaneous bone augmentation.
* Heavy smokers (\>10 cigarettes/day).
* Uncontrolled type 1 or 2 diabetes (HgA1c\>8).
* Known autoimmune or inflammatory disease.
* Serious blood disorders, such as hemophilia or leukemia.
* Local or systemic infection that may compromise normal healing (e.g., extensive periapical pathology).
* Liver or kidney dysfunction/failure.
* Currently receiving cancer treatment or within 18 months from completion of radio- or chemotherapy.
* Long-term history of oral bisphosphonates use (i.e., 10 years or more).
* History of intravenous bisphosphonates.
* Long-term (\>3 months) history of antibiotics or drugs known to alter the inflammation and/or immunological system 3 months before inclusion.
* Severe osseous diseases (e.g., Paget disease of bone).
* Pregnant women or nursing mothers.
* Not able or not willing to follow instructions related to the study procedures.
Pulse ACTH vs. MP for MS

We hypothesize that corticotropin or adrenocorticotrophic hormone (ACTH), administered as Acthar Gel® (MANUFACTURER NAME) is effective in the control of clinical disease activity as a pulse therapy for relapsing-remitting MS when added to standard treatment with beta-interferon.

We wish to determine whether ACTH, when administered as clustered monthly intramuscular injections (monthly pulse therapy) as add-on to beta-interferons, may be a safe and effective alternative to monthly pulse therapy with MP. In addition, we hypothesize that pulse therapy with ACTH alters immune function to favor a regulatory, rather than a pro-inflammatory T cell environment.

Please see the final manuscript

Eligibility Criteria:
Inclusion Criteria:

1. Clinically definite multiple sclerosis defined by McDonald Criteria.
2. Between 18-65 years of age.
3. Subject must able to understand and sign the IRB- approved informed consent form prior to the performance of any study-specific procedures and is willing to comply with the required scheduling and assessments of the protocol, including self-administration of study drug (if assigned to the ACTH arm).
4. Subjects who are women of childbearing potential, must have a negative serum pregnancy test at the screening visit, and must be willing to practice a reliable birth-control method.
5. Subjects must have at least one MS relapse within last year and/or at least one new T2 or Gadolinium-enhanced lesion on MRI while on stable interferon therapy.
6. EDSS (Expanded Disability Status Scale) score of 3.0 - 6.5
7. Currently on one of the approved beta-interferon drugs (Avonex, Betaseron, or Rebif) for a minimum of 6 months.

Exclusion Criteria:

1. Women who are either pregnant or breastfeeding, and women of child-bearing potential (defined as not surgically sterile or at least two years post menopausal) who are not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch, injectable or transdermal contraceptive, barrier method or sexual activity restricted to vasectomized partner.
2. Uncontrolled hypertension, clinically significant cardiac arrhythmias, gastrointestinal ulcer, uncontrolled diabetes mellitus, osteoporosis, any stage of renal failure, psychiatric disorders or any other clinically significant general health conditions that may interfere with the trial participation.
3. Subject has a history of drug or alcohol abuse within the past year.
4. Subject had corticosteroid treatment within last 90 days.
5. Subject started new medication within last 30 days.
6. Subject is on Tysabri treatment presently or within 6 months of screening.
7. Subject is on Novantrone, Cellcept, Rituxan or other chemotherapeutic treatment presently or within 6 months of screening.
8. Subject is a participant in another research project.
9. Subject has contraindications for either ACTH or MP administration.
Long Term Prophylactic Therapy of Congenital Long QT Syndrome Type III (LQT3) With Ranolazine

The purpose of this study is to determine whether ranolazine will reduce the risk of arrhythmic events in patients with long QT syndrome type 3.


Eligibility Criteria:
Inclusion Criteria:

* Long QT patients with genetic confirmation of carrier-status for the D1790G mutation in the SCN5A gene
* Corrected QT interval \> 460 msec

Exclusion Criteria:

* Need for therapy with medications that are potent or moderately potent CYP3A inhibitors (such as ketoconazole, diltiazem, verapamil, macrolide antibiotics or HIV protease inhibitors)
Biomarker Development in LGMD2i

The overall goal of this natural history study is to define the key LGMD2i phenotypes as measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker for LGMD2i to support therapeutic development.

Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due to missense mutations in the Fukutin-related protein (FKRP) gene. Patients develop progressive proximal muscle weakness that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and respiratory compromise.

There are promising new therapies that have been developed and as a result therapeutic trials are approaching.

The rationale for this study is to define appropriate COAs for LGMD2i, which will facilitate therapeutic development and ensure properly powered clinical trials. In addition, measurement of dystroglycan in muscles represents a potential muscle biomarker that could be used in early phase clinical trials as a measure of target engagement. The clinical utility of changes in dystroglycan has not been validated in human samples.

Eligibility Criteria:
Inclusion Criteria:

* Age between 10-65 at enrollment
* Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity)
* A genetically confirmed mutation in FKRP (LGMD2i)
* Willing and able to give informed consent and follow all procedures and requirements

Exclusion Criteria:

* Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
* History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant.
* Positive pregnancy test
* A 10-meter walk time of \<4 seconds