cyrilzakka/clinical-trials huggingface dataset:
Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome

The overall objectives are to explore the safety and efficacy of Reverse Transcriptase Inhibitors Tenofovir (TDF)/ Emtricitabine (FTC) administered in AGS affected children 2 to 18 years of age.

The investigators propose that a trial to assess the proof of principle that antiretroviral therapy through a drug combination of Tenofovir (TDF) and Emtricitabine (FTC) can decrease endogenous retroelement accumulation, and alter interferon signaling in Aicardi Goutières Syndrome (AGS) patients is reasonable and warranted at this time, based on existing in vitro and animal data. Additionally, this trial will further the investigators understanding of this disorder, measuring for the first time retroelements in human participants, exploring the retroviral burden in cerebrospinal fluid (CSF), the Interferon (IFN) signaling response, as well as evaluating antigen targets of autoimmunity and cytokines. If successful, this approach will clearly demonstrate the need for a larger trial of antiretrovirals in AGS with more clinically relevant outcomes.

Eligibility Criteria:
Inclusion Criteria:

* Molecular, neuroimaging, and clinical findings consistent with a diagnosis of AGS, with the exception of Double-stranded RNA-specific adenosine deaminase (ADAR1) and IFIH1, which are not postulated to result in nucleic acid accumulation
* Evidence of interferon activation such as elevation of CSF neopterin/tetrahydrobiopterin measured on the first evaluation.
* Ages 2-18 years (the age of 2 years is used because the drugs are FDA approved in children greater than 2 years)
* Weight of at least 10 kg
* Willingness to undergo serial lumbar punctures and blow draws for evaluation of laboratory based outcome measures
* Willingness to abstain from initiating the use of immune modulating therapies including corticosteroids
* Able to receive medications orally, by nasogastric (NG) tube or by Gastric (G)-tube
* No concomitant illness which would preclude safe participation as judged by the investigator
* Signed informed consent by the subject's legally acceptable representative
* Negative testing for HIV
* Negative testing for Hepatitis B
* Concurrent enrollment in the Myelin Disorders Biorepository Project (MDBP, ClinicalTrials.gov NCT03047369) and willingness to undergo associated procedures

Exclusion Criteria:

* Age \< 2 years or \>18 years
* Hepatic insufficiency with liver function tests greater than 3-times the upper limit of normal
* Renal insufficiency with creatinine clearance \<60
* Significant malabsorption
* Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at an additional risk by participating in this study
* HIV infection
* Hepatitis B infection
* Mutations in ADAR1 or IFIH1
Supporting Parents of Young Children With Type 1 Diabetes in Closed-Loop System

This study will examine the impact of a closed-loop insulin delivery system intervention on health and psychological outcomes in families with young children with Type 1 Diabetes (T1D).


Eligibility Criteria:
To be eligible for the study, a child must meet the following criteria since enrollment in the CEP 302 Trial:

1. Diagnosis of type 1 diabetes according to ADA diagnostic criteria
2. Time since diagnosis of at least six months
3. Age between 2.00 and 6.99 years at enrollment
4. Parental consent to participate in the study
5. Completion of the CEP 302 Trial and in the continuation phase of the Medtronic CEP 302 Trial using the Medtronic MiniMed 670G pump with Enlite3 sensor.

To be eligible for the study, a parent must meet the following criteria:

1. Parent or legal guardian of a child with type 1 diabetes meeting the "child" criteria outlined above.
2. Age of 18.0 years or older.
3. Parent comprehends written English.
4. Parent understands the study protocol and signs the informed consent document.

The presence of any of the following is an exclusion for the study (since enrollment in the CEP 302 Trial):

1. Child has a medical disorder that in the judgment of the investigator will interfere with completion of any aspect of the protocol (e.g., pregnancy, kidney disease, adrenal insufficiency, skin condition that may hinder sensor application).
2. Child has a neurologic disorder that in the judgment of the investigator will affect completion of the protocol
3. Current use of oral glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study
4. Child is unable to completely avoid acetaminophen for duration of study
Effect of Apical Enlargement to Different Preparation Sizes and Tapers on Pain and Bacterial Reduction in Necrotic Pulp

The aim of this prospective randomized clinical trial is to evaluate the effect of different apical size and taper preparation (35. 04; 35. 06; 45. 04 and 45. 06) on postoperative pain at 6, 12, 24, 48 and 72 hours, and intra-canal bacterial count in patients having mandibular premolars with necrotic pulps.

* Patients will be clinically and radiographically examined and their eligibility will be assessed. Eligible patients will be treated in one visit.
* Patients will be randomly assigned to one of 4 groups: experimental groups of root canal instrumentation with EdgeFile X7 to size #35/0.06 or #45/0.04 or #45/0.06 or the comparator group to size #35/0.04. Intra-canal bacterial count will be measured using a culture technique. Bacterial samples will be taken before and after root canal instrumentation. After endodontic treatment, patients will be given postoperative instructions and informed, in case of pain, to receive ibuprofen 400 mg as rescue medication.
* Postendodontic pain intensity and incidence at the different pain categories (No, mild, moderate, severe) will be assessed at 6, 12, 24, 48 and 72 hours postoperatively using Numerical Rating Scale (NRS).

Eligibility Criteria:
Inclusion Criteria:

* Systemically healthy patients, American Society of Anesthesiologists (ASA) I and II.
* Patient's age ranges between 18 to 35 years with no sex predilection.
* Patients with single-rooted mandibular premolars with asymptomatic necrotic pulp.
* Patients who can understand the Numerical Rating Scale (NRS).
* Patients able to sign informed consent.

Exclusion Criteria:

* Pregnant females.
* Mandibular premolars with periodontal pockets greater than 5 mm or greater than grade I mobility.
* Patients have a positive history of antibiotic use or analgesic use within the past week or required antibiotic premedication for dental treatment (such as prosthetic joint prophylaxis).
* Patients have teeth that have been previously accessed.
* Teeth with extensive crown destruction by caries that will not permit rubber dam placement.
* Teeth associated with acute periapical abscess, swelling or a fistulous tract.
* Radiographic evidence of external or internal root resorption vertical root fracture, perforation, calcification.
Treatment-Resistant Depression Registry

This registry will collect information about patients with treatment-resistant depression (TRD) who are currently in a major depressive episode. For the purposes of this study, TRD is defined as an ongoing depression lasting at least 2 years or that has recurred at least 3 times, to include the current episode, during the patient's lifetime AND has not adequately responded to 4 or more adequate antidepressive treatments. The registry will follow the clinical course and outcomes for patients with TRD who are treated with and without adjunctive (used along with other treatments for depression) vagus nerve stimulation (VNS) therapy.

Enrollment of TRD patients treated with VNS Therapy will consist of patients originally enrolled in the registry as well as patients who have completed the D-21 Dosing Study and are enrolled in the Registry for Long-Term Follow-up. Sites will maintain a screening log of all patients who have been screened for original TRD Registry patients.

Please note that because this is a post-approval registry, Cyberonics does not cover the cost of VNS Therapy implantation.

Eligibility Criteria:
Inclusion Criteria:

* Patient diagnosed with a current major depressive episode according to DSM-IV-TR criteria.
* For D-21 patients only who have completed the D-21 dosing Study without any D-21 inclusion and exclusion protocol deviation.
* Patient has been in the current depressive episode for 2 years or longer, or has had at least 3 lifetime episodes including the current MDE.
* Patient has had an inadequate response to 4 or more adequate antidepressive treatments.
* The patient has a CGI severity of illness score of moderately ill (score of 4) or greater.
* The patient must be able to provide informed consent and complete all forms.

Exclusion Criteria:

* Patient has a history of schizophrenia, schizoaffective disorder, any other psychotic disorder, or a current major depressive episode that includes psychotic features; or is currently psychotic.
* Patient is currently enrolled in a double blind investigational study; patients who have completed the double-blind D-21 study will be allowed to enter the Registry for Long Term Follow-up
* Other than those patients who were enrolled in the D-21 study, patient has previously received VNS therapy.
* Patient has a history of rapid cycling bipolar disorder.
Cyber-Human Systems for Personalized Well-being and Health

The purpose of the present study is to evaluate the effectiveness of using multi-parameter monitoring devices in the elderly to improve their quality of life not already understood as the absence of disease but in a logic that is intrinsically linked to the body-mind relationship, which is increasingly significant as biological age advances. The study will be conducted on a sample of volunteer elderly subjects who will wear devices capable of constantly monitoring vital parameters such as heart rate, physical activity, sleep quality, stress levels and higher level activities, linked sensory and cognitive aspects ecologically integrated with the elderly person's living environment, in the sense of an evaluative and qualitative focus on relationships within the person's area of action/interaction, possibly supported and stimulated by individualized and easily usable activities. The signals interpreted and returned by the technology to the elderly person who uses it can also act as a reassuring self-assessment of even normal body states, sometimes experienced as threatening and anxiogenic, thus stressful. The collection and management of these data may serve as a reference to the recognition of distress signals and complex experiences (e.g., depressive) that normally have significant effects on mental health, understood as intrinsically linked to the health of the body.


Eligibility Criteria:
Inclusion Criteria:

* healthy male and female aged 60 years and older
* signing of informed consent

Exclusion Criteria:

* chronic diseases
* cardiovascular disease
* presence of dementia and/or depression
* presence of confirmed paranoid or psychotic symptoms
Corneal Biomechanics and Corneal Reshaping Therapy

The aim of the proposed study is to investigate the predictive value of corneal biomechanical properties in corneal reshaping therapy and the role of these parameters in determining the amount of myopia reduction.

Experiment 1: To evaluate changes in corneal biomechanics caused by short-term corneal reshaping therapy.

Subjects will wear a conventional RGP lens in one eye, randomly selected, and an orthokeratology lens in the fellow eye, for 30 minutes, 60 minutes and one night, respectively. Corneal stiffness and tangent modulus will be measured before and after each wearing period.

Experiment 2: To evaluate changes in and the recovery of corneal biomechanics effected by long-term corneal reshaping and to assess whether corneal biomechanics can predict the rate of corneal reshaping.

Subjects will wear orthokeratology lenses for 6 months. Regular follow up visits (1 week, 1 month, 3 months and 6 months) will be arranged to monitor the changes in corneal stiffness and tangent modulus.

Eligibility Criteria:
Inclusion Criteria:

* Myopia between -4D to -5D, with-the-rule astigmatism not more than 1.5D, spherical equivalent between -4D to -5.75D, difference between two eyes within 1D, best corrected spectacle visual acuity 0.10 logMAR in each eye

Exclusion Criteria:

* previous corneal reshaping therapy, long-term contact lens wear, ocular disease
Postplacental Mirena IUD Insertion and Estimating Expulsion Rates.

This study aims to demonstrate that the expulsion rate is increased but acceptable when inserting Mirena IUDs immediately postpartum, termed 'postplacental IUD insertion'. The investigators will compare the postplacental insertion expulsion rate estimate with rates reported in the literature for 6 week postpartum insertion, which is currently the American standard for IUD insertion postpartum. Secondary outcomes will also be examined; endometritis, uterine perforation, continuation and pregnancy among others.

The average expulsion rate for 6 week postpartum IUD insertion is approximately 10-12% with a range between 3-20% at 1 year. An acceptable expulsion rate for postplacental insertion (PPI) has not been defined and varies between studies. There are limited data on the expulsion rates of levonorgestrel intrauterine systems. Expulsion rates range widely from 1-3% to as high as 30-40% depending on the IUD and the study. Studies report an average rate of expulsion in ranges approximating 10-12%, similar to 6 week insertion rates.

There are many limitations to published studies including the use of older model IUDs no longer in use, multiple insertion techniques that have been deemed ineffective in reducing expulsion rates as well as varying follow up times making comparison of expulsion rates difficult.

Eligibility Criteria:
Inclusion Criteria:

* age 18 or greater
* obstetric patient in greater Portland, ME area

Exclusion Criteria:

* Evidence of chorioamnionitis (persistent fetal tachycardia, intra-partum fever \>38.0)
* prolonged rupture of membranes (greater than 24 hours)
* intrauterine fetal demise
* use of general anesthesia at time of delivery
* postpartum hemorrhage (\>500ml vaginal, \>1000ml cesarean)
* magnesium administration in labor due to HELLP syndrome or preeclampsia
* preterm delivery.
Severe CAV MRI in Heart Transplant Recipient

Hypothesis: CAV is associated with fibrotic changes on cardiac MRI, altered levels of pathogenetically-related biomarkers, and specific RNA expression changes in the blood

Cardiac allograft vasculopathy (CAV) is a major limitation to longevity after heart transplantation (HT), accounting for almost 30% of deaths after year 5. The only cure is re-transplant which is associated with a 30-day mortality of 30%, and raises ethical issues due to limited resources. Standard preventive measures, such as statin therapy, have limited success due to the multi-factorial nature of the process and influence of transplant-specific risk factors. Consensus regarding the management of CAV is lacking due to the absence of prospective studies evaluating timing of initiation of therapy, effect of therapies on long-term outcomes, and effective diagnostic strategies. Primary prevention of CAV, which will be evaluated in the proposed study, could improve longevity of heart transplant recipients and optimize use of a limited resource.

The current gold standard for evaluation of CAV is surveillance coronary angiogram, which is highly insensitive, particularly in early disease. Intravascular ultrasound (IVUS) is the most sensitive tool for the diagnosis of CAV, providing specific information such as the appearance and thickness of the intima and media, however it is not widely used in the clinical setting. Physiologic studies of the coronary arteries are also useful in assessing risk, but are not practical in a clinical setting. These invasive studies expose the heart transplant recipient to radiation, nephrotoxic contrast, and potential vascular complications. During the evolution of CAV, there are important structural, functional, and genomic changes that occur in parallel and possibly before.

Study Objectives

1. Determine the structural, functional and genomic changes associated with severe CAV
2. Identify novel and noninvasive markers of CAV

Study Design This is a cross-sectional study which will evaluate structural, functional and genomic changes associated with severe CAV in heart transplant recipients within 15 years of transplant. 30 heart transplant recipients identified via our study database and the transplant clinic will be enrolled into the study. We will enroll 15 heart transplant patients with severe CAV and 15 without CAV.

Subjects will undergo a one-time assessment of radial artery elasticity, blood draw for gene expression profiles, and cardiac MRI.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years
* Provide informed consent
* Successful orthotopic heart transplant within 15 years of enrollment

Exclusion Criteria:

* Chronic kidney disease with creatinine \>2.5 mg/dl
* Ejection fraction \<45% if CAV or \<50% if no CAV
* IV contrast allergy or reaction (gadolinium)
* Active infection (febrile illness, cytomegalovirus or other significant infection)
* Treated humoral rejection or cellular rejection grade 3A/2R or greater within 3 months
* Contraindication to MRI
Evaluation of Pain Trajectories After Surgery and Their Potential Relationship With Chronicity at 3 Months

The effective management of acute postoperative pain remains a daily challenge despite the organizational efforts made and the techniques put in place.

Thirty percent of patients who undergo surgery suffer from chronic post-surgical pain, of which 5 to 10% are of severe intensity. Many preoperative, intraoperative, and postoperative factors, related to the patient, the surgical procedure, or the anesthetic technique, have been incriminated as risk factors for chronic post-surgical pain. The severity of acute postoperative pain is recognized as one of the risk factors for the occurrence of chronic post-surgical pain on which we can hope to interact during the peri-operative period.

In this cohort study, we wish to define the typologies of postoperative pain trajectories observed from Day 0 to Day 7 and to estimate the proportion of patients with an abnormal resolution of pain in a model of organization such as that of our institution, in classic hospitalization and in ambulatory care.


Eligibility Criteria:
Inclusion Criteria:

* The patient must be insured or beneficiary of a health insurance plan
* The patient is available for 3 months of follow-up
* The patient has undergone a planned surgical procedure in one of the participating departments
* The patient is willing and able to respond to the study questionnaires

Exclusion Criteria:

* The patient is participating in another study
* The patient is in an exclusion period determined by a previous study
* The patient is under judicial protection, under tutorship or curatorship
* It is impossible to correctly inform the patient
* Patient admitted to the ICU and still intubated at day 1
Comparison of Two Miniscrew Anchored Maxillary Protraction Protocols

This study evaluates the dentoskeletal effects produced by two maxillary protraction protocols in adolescent patients. Half of participants will be treated with a tooth-borne and tooth-bone-borne expanders as anchorage in the maxillary arch. Miniscrews will be used as anchorage in the mandibular arch for both groups.

Class III malocclusion treatment in growing patients is challenging. A new treatment for maxillary protraction using skeletal anchorage reported an efficient maxillary protraction in the late mixed dentition an early permanent dentition. Therefore, the aim of this study is to compare the dentoskeletal effects produced by two maxillary protraction protocols anchored on miniscrews.

The sample will be recruited at the Orthodontic Clinic of Bauru Dental School, University of São Paulo, Brazil. A sample of thirty-five patients, between 9 and 13 years old will be selected. The inclusion criteria are: Class III malocclusion associated with anterior crossbite. The participants will be allocated into 2 groups. Group 1 will comprise 20 individuals treated with a tooth-bone-borne expander and 2 miniscrews in the mandible Group 2 will comprise 15 individuals treated with a tooth-borne expander and 2 miniscrews in the mandible. Digital models and cone-beam computed tomography (CBCT) will be obtained before (T1) and 12 months after treatment (T2). Occlusal radiographs and partial (canine to canine) models will be obtained before and immediately after expansion. Two-dimensional cephalometric evaluations will be performed in the Dolphin® software. The arch width, arch perimeter and arch length will be analyzed with the Orthoanalyzer® software. Three-dimensional superimposition at the cranial base of T1 and T2 CBCT images will be performed. The inter incisor diastema will be evaluated by occlusal radiographs and dental models. Discomfort, pain and quality of life will evaluated by questionnaires. After verifying the normal distribution, the intragroup comparison will be performed with paired t test and intergroup comparison will be performed with t test. In the case of lost to follow-up patients, intention to treat analysis will be used. A significance level of 5% will be regarded for all tests.

Temporary pain and discomfort are possible after the installation of the miniscrews. Patients and legal guardians will be informed. After the consent, the treatment can be stoped at any time.

Eligibility Criteria:
Inclusion Criteria:

* Both sexes;
* Ages ranging from 9 to 13 years old;
* Class III malocclusion;
* Mandibular canines erupted.

Exclusion Criteria:

* Previous orthodontic treatment;
* Cleft lip and palate;
* Craniofacial syndromes;
* Systemic and/or neurological diseases.
Impact Nerium Oleander on Immune Function

Assess the impact of a proprietary extract of Nerium oleander on immune function as evidenced by COVID-19 symptoms and mortality in COVID-19 positive patients and their close contacts compared to controls that did not receive the extract.

This is an exploratory study based on positive in-vitro, and in-vivo (humans) that appear to support an immune function benefit. Up to 100 patients that are COVID-19 positive in the ambulatory setting will be invited to participate. After informed consent is obtained, patients will be in either the Intervention Group (receive extract) or Comparison Group (did not receive extract). A baseline assessment and record review will be conducted to assure eligibility criteria. Patients in the Intervention Group will be given .5 ml (6.25 mg of extract) every 6 hours for 5 days, total of 25 mg per day / 125 mg for 5 days. Patient vital signs (temperature, pulse oximetry, blood pressure) and CDC symptoms / side effects will also be tracked. A dedicated medical oversight team with 24 / 7 access to care will be provided to monitor safety and tolerance. Patients will be followed for 10 days. Baseline antibody, RT-PCR, and live virus will be collected on Day 1, Day 5, and Day 10. A Data Monitoring Committee at the Schull Institute will meet weekly to review data.

Eligibility Criteria:
Inclusion Criteria:

* Age 18
* COVID 19 positive or close contact of COVID 19 positive
* No use of cardiac glycosides or other antiarrhythmic medications

Exclusion Criteria:

* No use of cardiac glycosides or other antiarrhythmic medications
* No allergy to coconut oil