cyrilzakka/clinical-trials huggingface dataset:
An Investigation of Tumor Necrosis Factor (TNF)-Alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

We have developed in vitro systems including primary epithelial cell cultures and explant cultures of bronchial tissues to study the interaction between the bronchial mucosa and allergens. This approach involves culturing bronchial biopsies under optimal conditions and stimulate them with allergens thus enabling us to perform a dynamic study without the need of performing several bronchoscopies and will allow the testing of unapproved substances, which could, otherwise, not be delivered, in vivo.

We wish to apply these ex vivo bronchial culture systems to assess cytokine release in moderately severe asthmatics and evaluate the effects of blocking TNF-alpha signalling using anti TNF-alpha monoclonal antibodies.

Volunteers with moderately severe asthma will be recruited and carefully characterized in terms of lung function, asthma symptom scores, medication usage and allergen sensitivity (by blood and skin tests). If suitable, they will then be asked to withdraw their corticosteroids for a week with careful monitoring of the symptoms and peak flows before undergoing fibreoptic bronchoscopy as was carried out in the previous explant study. Bronchial brushings and biopsies will be carried out as per standard technique used in University medicine. Primary epithelial cell cultures will be established from bronchial brushings and will be used for optimising the dose of anti TNF-alpha required for inhibition of TNF-alpha induced responses. The biopsies will be placed in either culture medium alone, allergen extract or allergen extract plus anti TNF-alpha antibody and cultured for 24 hours. The biopsies will then be either snap frozen in liquid nitrogen for analysis of cytokines or processed for immunohistochemical analysis. The supernatants from each study will be recovered and analysed for cytokine (IL-5, IL-8, IL-13, MIP 1 alpha and RANTES) release by ELISA.

Eligibility Criteria:
Inclusion Criteria:

* Moderately severe asthmatics
* Male or female
* Uses inhaled beclomethasone 400-1000 mcg or equivalent
* Documented positive skin test to common allergens and
* FEV1 of \>60% predicted

Exclusion criteria:

* Smokers
* Subjects with an acute asthmatic episode in the last 6 weeks
* Other significant clinical illnesses
* Pregnant women
* Those sensitive to lignocaine
CyclASol® Phase 1 Study

This study is intended to investigate the tolerability and the safety of Cyclosporine A containing CyclASol® eye drops compared to Placebo (vehicle) in a cohort of healthy volunteers. Subjects will be randomly assigned to dosing with CyclASol® eye drops or Placebo (vehicle) in the first part (first period) of the study, and switched to the alternative dosing in the second part (second period) of the study. An ophthalmological assessment of the eyes will be performed, and a questionnaire will be issued in the beginning and after each dosing. Additionally physical examinations, safety laboratory and ECGs will be performed, and blood samples will be analyzed for Cyclosporine A and Placebo (vehicle).


Eligibility Criteria:
Inclusion Criteria:

* Healthy male or female subject aged 18 - 45 years
* Nonsmoker, for at least three months prior to first dose of trial medication
* BMI from 18.5 to 29.9 (kg/m2)
* Corneal/Conjunctival staining Oxford grading = 0°
* Schirmer I more than 10 mm/5min
* Tear Film Break-Up Time (TFBUT) equal or more than 10 s
* Intra-ocular pressure between 10 and 20 mmHg
* Normal funduscopy
* Subject will have given their voluntary written informed consent to participate in the study in their own language and are willing to comply with the protocol

Exclusion Criteria:

* History of clinically relevant allergy (except for untreated, asymptomatic, seasonal allergies at time of dosing)
* History of dry eye disease, ocular surgery, corneal disease
* Known hypersensitivity to the drug substance
* Limbal stem cell deficiency
* Cicatricial pemphigoid
* Glaucoma or known steroid response on intraocular pressure
* Ocular allergy or incompatibility against Ciclosporin or semifluorinated alkanes
* Punctual occlusion
* Corrected vision with glasses less than 0.7 on one or both eyes
* Contact lens wear 3 weeks before to the planned first drug administration and/or during the study
* Acute infection of ocular surface (bacterial, viral, fungal...)
* Acute trauma of ocular surface
* No acceptable methods of birth control
* Pregnancy or breast-feeding period (females only)
* Use of any drugs whatsoever (including vitamins and herbals) for fourteen (14) days prior to the planned first drug administration (excluding contraceptives in women and single use of paracetamol or ibuprofen)
* Topical or systemic therapy with steroids, Ciclosporin, non-steroidal anti- inflammatory drugs, tetracyclines or other immunomodulatory substances within last 90 days prior to the planned first drug administration or during this trial
Entire Papilla Preservation Technique With and Without Biomaterials in the Treatment of Isolated Intrabony Defects

The aim of this study is to investigate the clinical efficacy of entire papilla preservation technique with and without the adjunct of amelogenins (EMD) and bone substitutes.

The present study is designed as a single-centre, parallel group, randomized, controlled clinical trial comparing the efficacy of EPP with or without biomaterials. Each patient will contribute with a single intrabony defect. Three months after completion of initial periodontal therapy, all the experimental sites will be accessed with the "EPP" technique (Aslan et al., 2017a) and carefully debrided. EDTA gel will be applied on the instrumented root surfaces. A combination of EMD and deproteinized bovine-derived bone substitute will be applied in the test group (EPP EMD + BS), while the control group (EPP) will not receive any regenerative biomaterial. Patients will be enrolled in a stringent maintenance programme with recalls on a weekly basis for the first month and then monthly controls for professional tooth cleaning up to 1 year. Clinical parameters will be recorded immediately before regenerative surgery (baseline) and 12 months after the regenerative periodontal surgery.

Eligibility Criteria:
Inclusion Criteria:

* Systemically healthy
* Clinical diagnosis of advanced periodontitis
* Having one isolated intrabony defect with probing depth (PD) ≥7 mm, clinical attachment level (CAL) ≥8 mm and at least 4 mm intrabony component involving predominantly the interproximal area of the affected tooth.
* Full-mouth plaque score (FMPS) ≤20%.
* Full-mouth bleeding score (FMBS) ≤20%.

Exclusion Criteria:

* Smokers
* Patients with known systemic diseases such as diabetes and cardiovascular diseases or using medications that affect periodontal tissues, pregnant or lactating women
* One-wall intrabony defects
* Defects that involve buccal and lingual sites
* Presence of inadequate endodontic treatment and/or restoration in the relevant teeth.
Use of Sildenafil for Treatment of Urinary Incontinence

The investigators goal is to develop medical treatments for stress/mixed urinary incontinence. Sildenafil has been shown to improve blood flow as well as muscle mass and strength and to decrease muscle fatigue. The investigators believe that it will improve muscular atrophy in the pelvic floor, thus improving symptoms of urinary incontinence related to pelvic floor dysfunction.

Aim: To determine the effect of sildenafil on urinary incontinence.

1. Episodes of urinary incontinence will be recorded using a 3 day bladder diary.
2. Quantitative assessment of urinary incontinence will be performed at baseline and after treatment using a Pad Test.
3. Muscle strength will be assessed through use of a perineometer.
4. To evaluate macrocirculatory blood flow in pelvic organs, women will be assessed with noninvasive imaging before and after randomization to sildenafil.
5. Secondary outcomes will include evaluation of muscle and vaginal mucosal thickness.

Eligibility Criteria:
Inclusion Criteria:

* Postmenopausal females, 50-80 years of age, at the time of consent
* Have stress or mixed urinary incontinence, with at least 3 episodes/week
* Willing and able to comply with study procedures
* Willing and able to provide written informed consent

Exclusion Criteria:

* Significant heart, liver, kidney, pulmonary, blood, autoimmune or peripheral vascular disease (history of Hashimoto's thyroiditis is not exclusionary if stable and thyroid replacement is being administered. Thyroid testing will be performed at screening and as needed during study visits. )
* Systolic blood pressure \<100 or \>150, diastolic blood pressure \<60 or \>90 after repeated evaluation with proper cuff. This range is smaller than the acceptable range stated in the prescribing information for sildenafil (\>90/50 and \<170/110)
* Diabetes mellitus or other untreated endocrine disease
* Active cancer
* Currently using and planning to continue use of urinary incontinence medications during study period
* BMI \> 40
* HIV, Hepatitis B, or Hepatitis C
* Use of systemic nitrates, anabolic steroids or corticosteroids in the past 6 months
* Use of alpha blockers
* Any medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation.
* Known allergic reaction to any agent under investigation or required by the protocol.
* History of prior non-compliance or the presence or history of psychiatric condition (including drug or alcohol addiction) that would, in the opinion of the investigator, make it difficult for the subject to comply with the study procedures or follow the investigators instructions.
* Females who are pregnant or lactating.
Immunogenicity and Safety of Tetraxim Versus Local DTP + IPV

The present clinical study will assess the immunogenicity and reactogenicity of Sanofi Pasteur's DTaP-IPV combined vaccines as a three-dose primary vaccination at 2, 4 and 6 months of age compared to commercially available vaccines in order to meet the requirements for registration of the product in South Korea.

Primary objective To demonstrate the non-inferiority in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3) and seroconversion/vaccine response rates to Pertussis antigens (PT, FHA) of Sanofi Pasteur's DTaP-IPV combined vaccine versus commercially available Biken's DTaP (CJ purified PDT vaccine ™) and Aventis Pasteur's IPV (IMOVAX POLIO) monovalent vaccines, one month after the three-dose primary vaccination.

Secondary objectives

1. Immunogenicity: To assess the non-inferiority in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3) and seroconversion / vaccine response rates to Pertussis antigens (PT, FHA) of Sanofi Pasteur's DTaP-IPV combined vaccine versus historical reference (Study E2I03294 - France). To assess and describe the immunogenicity of the study vaccines in both groups.
2. Safety: To assess and describe the safety of the study vaccines after each dose.


Eligibility Criteria:
Inclusion Criteria:

* Aged 56 to 70 days inclusive on the day of inclusion
* Born at full term pregnancy (\>37 weeks) with a birth weight ≥ 2.5 kg
* Informed consent form signed by the parent(s) or other legal representative
* Able to attend all scheduled visits and to comply with all trial procedures

Exclusion Criteria:

* Participation in another clinical trial in the 4 weeks preceding the (first) trial vaccination
* Planned participation in another clinical trial during the present trial period.
* Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy.
* Systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or a vaccine containing the same substances.
* Chronic illness at a stage that could interfere with trial conduct or completion.
* Blood or blood-derived products received in the past or planned administration during the trial (including immunoglobulins).
* Any vaccination in the 3 weeks preceding the first trial vaccination.
* History of diphtheria, tetanus, pertussis, poliomyelitis infection (confirmed either clinically, serologically or microbiologically).
* Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis diseases with the trial vaccine or another vaccine.
* Thrombocytopenia or a bleeding disorders contraindicating intramuscular vaccination
* History of major neurological diseases or seizures.
* Febrile illness (rectal temperature ≥ 38.0°C or axillary temperature ≥ 37.4°C) on the day of inclusion.
* Known family history of congenital or genetic immuno-deficiency.
Controlled Study of ONO-5920 in Patients With Involutional Osteoporosis in Japan

The purpose of this study is to evaluate the efficacy and safety of ONO-5920 in patients with involutional osteoporosis.


Eligibility Criteria:
Inclusion Criteria:

1. A diagnosis in accordance with Criteria for the Diagnosis of Primary Osteoporosis.
2. Other inclusion criteria as specified in the study protocol.

Exclusion Criteria:

1. Patients having secondary osteoporosis or another condition that presents low bone mass.
2. Patients having findings that affect measurement of lumbar spinal bone mineral density by DXA
3. Patients that have been administered bisphosphonate derivatives.
4. Other exclusion criteria as specified in the study protocol.
Self-Management Interventions for Long COVID-19

The purpose of this study is to investigate and compare the feasibility and efficacy of two group-based interventions (education vs. mindfulness) to help self-manage Long-COVID symptoms.

After a COVID-19 infection, more than 75% of patients report ongoing somatic, cognitive, and psychiatric symptoms. At this time, research is needed to help develop treatments that limit the impact of these symptoms on people who have had COVID-19. The present study investigates the feasibility and efficacy of two group-based interventions in a single-centre, 3-arm, pragmatic RCT comprising (i) an Education Intervention Group arm, (ii) a Mindfulness Skills Intervention Group arm, and (iii) a No-Treatment Control Group arm. Phase 1 is a pilot RCT and will employ a mixed methods design with qualitative post-treatment interviews in a subset of participants in the Education Intervention Group arm only. Phase 2 is a full-scale, quantitative-only RCT, with refinements and power analysis based on the results of Phase 1. Sessions of both groups are delivered by licensed therapists and clinicians. Sessions last 1.5 hours per week for 8 weeks, with 10-15 patients/group in an online format. The Education group participants will learn about the nature of Long-COVID symptoms and discuss strategies for self-care/self-management of symptoms in recovery. The Mindfulness Skills Intervention group participants will receive an introduction to some basic mindfulness skills and practice strategies such as Mindfulness of Breath, Body, Sounds, Thoughts, and Choiceless Awareness.

Eligibility Criteria:
Inclusion Criteria:

* Clinically diagnosed Long-COVID plus PCR positivity with and without hospitalization
* 3-12 months post-diagnosis of COVID-19
* \>2 self-reported persisting symptoms in \>1 mood, cognitive and/or somatic symptom domain
* Age \>18
* English speaking
* Private access to computer/internet

Exclusion Criteria:

* Acute ventilator support
* Diagnosed dementia
* Past/present history of psychotic illness or mania and, because of potential overlap in symptoms, diagnosis of chronic fatigue syndrome, fibromyalgia, chronic lyme disease or traumatic brain injury
* Long-COVID symptom severity (i.e., physical, cognitive, emotional symptoms) at a level that would significantly interfere with attendance/adherence to the intervention protocol
Ketogenic Diet Compliance in Patients Affected by Locally Advanced Rectal Cancer Patients Who Undergo to Radiotherapy

Patients with locally advanced non-metastatic adenocarcinoma of the rectum undergoing chemoradiation therapy will be assigned to 2 groups:

* the intervention group will be prescribed an individualized ketogenic eating plan to be followed throughout the treatment period
* the control group will be prescribed a diet therapy plan treatment following the international guidelines of clinical nutrition, also to be followed during treatment

Some days before the start of radiotherapy there will be the first visit in which patients will be enrolled and placed in one of the following two groups:

* The intervention group (KD) will be prescribed a ketogenic diet therapy plan characterized by the following composition: carbohydrates \< 30g/day, 1.2g-1.5g protein/kg/day and lipids \> 65%.
* The control group (SD) will be prescribed a nutrition plan based on the Mediterranean diet model according to ESPEN guidelines (carbohydrates 45-55%, protein 15-20% and lipids 30-35%) There will then be two additional follow-ups for patients: one during the period of therapy and one at the end of therapy.

Compliance with diet therapy treatment (SD vs. KD) will be assessed by analysis of a food diary that the patient will be asked to complete.

During follow-ups it will be assessed:

* BMI and body composition (by bioimpedance analysis)
* Muscle strength and physical performance (by hand grip test and sit-to-stand test) Compliance with and toxicity of radiochemotherapy treatment will be assessed at the radiochemotherapy visits (3 visits during treatment)

Eligibility Criteria:
Inclusion Criteria:

* Histologic confirmation of rectal adenocarcinoma
* Locally advanced rectal cancer
* Patients undergoing neoadjuvant radiotherapy treatment
* Signature of informed consent to the processing of personal data

Exclusion Criteria:

* Severely malnourished patients according to GLIM (Global Leadership Initiative on Malnutrition) criteria
* Patients treated for palliative purposes
* Patients with metastatic disease
* Diabetes mellitus
* Pregnancy or lactation
* Significant food allergies that would make the person unable to consume the food provided
* Refusal to participate in the proposed clinical trial
Ventilator Hyperinflation and Hemodynamics

Ventilator hyperinflation (VHI) has been shown to be effective in improving respiratory mechanics, secretion removal, and gas exchange in mechanically ventilated patients; however, the literature is scarce concerning its safety and adverse effects. Thus, the aim of this study is to compare the hemodynamic repercussions of VHI in volume-controlled mode. In a randomized, controlled and crossover design, 24 mechanically ventilated patients will undergo 2 modes of ventilator hyperinflation (with and without an inspiratory pause) and a control intervention. Cardiac output, cardiac index, mean arterial pressure, pulmonary vascular resistance, systolic volume and other hemodynamic variables will be recorded during the interventions.

Background: ventilator hyperinflation (VHI) has been shown to be effective in improving respiratory mechanics, secretion removal, and gas exchange in mechanically ventilated patients; however, the literature is scarce concerning its safety and adverse effects. Thus, the aim of this study is to compare the hemodynamic repercussions of VHI in volume-controlled mode.

Methods: in a randomized, controlled and crossover design, 24 mechanically ventilated patients will undergo 2 modes of ventilator hyperinflation (with and without an inspiratory pause of 2 seconds) and a control intervention. For the VHI interventions, the inspiratory flow will be set at 20 Lpm, and tidal volume will be increased until a peak pressure of 40cmH2O is achieved. During the control intervention, the patients will remain in volume-control ventilation with an inspiratory flow = 60Lpm and tidal volume = 6mL/IBW. The interval between interventions (washout) will be of 10 minutes or more, according to the time needed to recover the cardiac index to baseline values (maximum difference of 10%). Cardiac output, cardiac index, mean arterial pressure, pulmonary vascular resistance, systolic volume and other hemodynamic variables will be recorded during the interventions by using impedance cardiography.

Eligibility Criteria:
Inclusion Criteria:

* Patients under mechanical ventilation for more than 48h

Exclusion Criteria:

* mucus hypersecretion (defined as the need for suctioning \< 2-h intervals),
* absence of respiratory drive,
* atelectasis,
* severe bronchospasm,
* positive end expiratory pressure \> 10cmH2O,
* PaO2-FiO2 relationship \< 150,
* mean arterial pressure \< 60mmHg,
* inotrope requirement equivalent to \>15 ml/h total of adrenaline and noradrenalin,
* intracranial pressure \> 20mmHg
At Work and Coping - Effect Study of Workcoping for Patients With Anxiety and Depression

Mental disorders, mainly various anxiety and depressive disorders, are an increasing reason for sick leave and disability pension. Cognitive behaviour therapy (CBT) has been shown to have an effect on anxiety and depression, but the investigators know little about this in relation to employment. Close follow-up in ordinary employment increase employment participation for serious mental illness, but this is not yet investigated to the same degree for lighter mental disorders.

Center for Work-Coping (No: "Senter for Jobbmestring" - SJM) combines Cognitive behaviour therapy (CBT) and individual placement and support (IPS) and facilitation of work for people with anxiety and depression who are in danger of falling out of work.

The purpose of this project is to evaluate the effectiveness of the model in SJM. The effect will be evaluated through a randomized controlled trial (RCT) in which participants will be randomized to SJM or regular follow-up by The Norwegian Labour and Welfare Administration (NAV) or by their regular general practitioners (GP) and self-help resources. The main outcome measures are work participation with changes in mental health as a secondary outcome.


Eligibility Criteria:
Inclusion Criteria:

* Problems coping with work due to psychological illness (anxiety and depression)
* Reasonable closeness to work (possible to return within a year)

Exclusion Criteria:

* Other reasons as primary cause of work problems
* Serous psychiatric disorders
* Suicide risk
* Pregnancy
* Ongoing psychological treatment (therapy)
* Ongoing substance abuse