cyrilzakka/clinical-trials huggingface dataset:
Effect of SNPs in the BCMO1 Enzyme

Summary:

Chronic intake of foods low in vitamin A (retinol) and provitamin A forming an unbalanced diet with little variety is common in young individuals in the United Kingdom (UK) population and can lead to subclinical micronutrient deficiency. Provitamin A sources such as β-carotene are cleaved centrally by the β-carotene 15,15'-monooxygenase (BCMO1) into retinal, the precursor of retinol. However, the amount of β-carotene and retinol produced after ingestion of β-carotene is highly variable between healthy individuals, with approximately 40% of the subjects being classified as low responders. Several stable isotope studies have shown a large disparity between the most efficient converters and the most inefficient converters of β-carotene with variations of up to 8-fold. It is possible that differences in β-carotene response may be due to single nucleotide polymorphisms (SNPs) in genes involved in aspects of β-carotene conversion. Previous work has shown that carriers of both, the 379V and 267S+379V BCMO1 variant alleles had a reduced ability to convert β-carotene. More importantly, 44% of the western population have the 379V haplotype. A high percentage of the Western population may therefore not be able to achieve adequate vitamin A intake if dietary β-carotene is a major source of their vitamin A intake. This is of particular relevance to vegetarians, to young individuals aged 19-24 years who have lower intakes of preformed retinol than any other age group, and to pregnant women. The aim of this study is to establish whether the maximum recommended dose for β-carotene of 7mg/day by the British Expert Committee on Vitamins and Minerals (EVM) can overcome the SNP effect in the BCMO1 enzyme.

Hypothesis:

The investigators hypothesize that the current maximum recommended intake of 7 mg of β-carotene per day cannot overcome the low convertor phenotype in BCMO1 to fulfill vitamin A requirements in these people.


Eligibility Criteria:
Inclusion Criteria:

* Healthy individual.
* Female.
* Between 18 and 45 years of age.
* Caucasian.
* BMI between 18 and 30 kg/m2.
* Subject willing and able to give written informed consent.

Exclusion Criteria:

* Smoking.
* Diabetes.
* Gastrointestinal diseases.
* Renal and hepatic diseases.
* Hyperlipidaemia.
* Preformed dietary retinol intake above 60% of reference nutrient intake (RNI) values.
* Recreational drug use.
* Multi-vitamin consumption.
* Pregnancy.
* Menopause.
* Allergy or sensitivity to study products or ingredients.
* Blood donation 3 months prior to screening.
* Participation in other clinical study 4 weeks prior to study start.
* Suspected inability or unwillingness to comply with study procedures.
Fluid Responsiveness and Venous Congestion Evolution During Volume Expansion

Fluid responsiveness is a critical determinant guiding fluid therapy in critically ill patients. However, excessive fluid administration can result in fluid overload, leading to venous congestion and worse clinical outcomes. Venous congestion, a marker of impaired fluid clearance, is increasingly recognized as a significant contributor to poor prognosis. Previous studies have demonstrated the coexistence of fluid responsiveness and venous congestion in critically ill patients. Notably, these studies were limited by the absence of fluid challenge-the gold standard for assessing fluid responsiveness-leaving the dynamic relationship between fluid responsiveness and venous congestion incompletely understood. This study aims to investigate the interplay and temporal evolution of fluid responsiveness and venous congestion following a standardized fluid challenge in critically ill patients.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years
* Hospitalized in the intensive care unit (ICU)
* Hemodynamic monitoring in place, with a pulse wave contour analysis- derived estimation of cardiac output (either calibrated or uncalibrated)
* Decision made by clinicians to perform volume expansion through intravenous infusion of crystalloid fluid

Exclusion Criteria:

* Pregnancy
* Refusal to participate by relatives of the patient or the patient himself
Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations

The aim of the study is to analyze the esthetic outcome of the first surgical repair of cleft lip and palate (CLP) patients.

The aim of the study is to identify differences in the aesthetic evaluation of full-face and nasolabial region 3-D images of CLP patients following primary lip repair by laypeople.

The management of cleft lip and palate patient's generally involves the soft palate reconstruction as well as the repair of lip and nasal soft tissue defects.

From an esthetic point of view, the primary repair, usually performed between 9 and 18 months of age, prepares the patients to grow into childhood and succeed in life without focusing on their deformity.

An increasing number of outcome measure rating systems has been raised, suggesting a lack of consensus to a reliable, validated and reproducible scoring system for facial aesthetics in cleft patients. Many templates and lay panel scoring systems have been described, yet never fully validated. Advanced 3D imaging technologies may produce validated outcome measures in the future, but presently there remains a need to develop a robust method of facial aesthetic evaluation based on standardised patient photographs.

The aim of the study is to to determine and compare the level of agreement among examiners' subjective aesthetic evaluation of full-face and nasolabial region 3-D images of CLP patients following primary lip repair by laypeople, developing some recommendations for a consistent scoring protocol.

Eligibility Criteria:
Inclusion Criteria:

* age, between 20 and 25 years
* sex, in order to have at least 25 male and female raters
* sociocultural status: the layperson panel includes undergraduate students without extensive professional knowledge on cleft lip and palate patients

Exclusion Criteria:

* previous participation in research studies
* familiarity or close friendship with cleft lip and palate patients
* lack of blindness about the study protocol (it could bias the reported results)
Study of Locomotor Expectations for Ascending/descending Slope and Stairs in Patients with Limb Amputations

Patients with lower limb amputations are equipped with prostheses that can be mechanical and/or electronic. These prostheses can be mono-articular (only the ankle) or bi-articular (knee and ankle for example). For amputee patients, situations that may seem trivial, such as climbing and descending stairs, become complex. Thus during the descent of stairs, an unamputated person will slow down the descent by contracting the thigh muscles, which are obviously lacking in the amputee patient. Current prostheses, known as "intelligent" (or "microprocessor") prostheses, make it possible to adjust the locomotion only once the first step has been taken and to assist the patient during ascent/descent situations on slopes and stairs. The next technological challenge in the development of lower limb equipment is to be able to anticipate these complex environmental situations, in order to secure and facilitate movement even before the obstacle is crossed or the terrain changed.

This project plans to use the locomotor expectations commonly made during walking as a means of regulating the locomotor pattern. We believe that these expectations will depend on the situation, i.e. a particular anticipation when climbing or descending a slope, or when approaching a staircase, etc. To understand and describe these locomotor expectations, we plan to use recent techniques called supervised machine learning. These will make it possible to classify locomotor behaviour when walking on a slope or stairs. In the second phase, we would like to describe precisely the characteristics of the movements of the joints, and of the muscles during these adaptations. The final objective of this work is to create an autonomous sensor system to control the anticipatory behaviour of a lower limb prosthesis.


Eligibility Criteria:
Inclusion Criteria:

Healthy volunteers:

* person who has given oral consent
* male or female adult
* person being able to understand simple orders, locomotion instructions

Lower limb amputee patients:

* person who has given oral consent
* male or female adult
* patient with unilateral major lower limb amputation of any origin (traumatic, vascular, infectious, congenital or neoplastic) with definitive equipment used routinely for at least 3 months.
* person able to understand simple orders, locomotion instructions

Exclusion Criteria:

* person not affiliated or not benefiting from a heath insurance system
* person subject to a legal protection measure (curatorship, guardianship)
* person with a legal guardian
* pregnant or breastfeeding woman
* adult unable to consent
* person with a dislocated hip
* subject with conditions or disabilities other than amputation that affect walking
Pharmacogenomics of Mood Disorder in Chronic Kidney Disease Patients

By using genetic information we could predict the prevalence of mood disorder and response to treatment.

This prospective cohort study enrols patients with chronic kidney disease and gathers genetic information. By the patient's biochemical information, including genetic information, we could predict the prevalence of mood disorder and response to the antipsychotherapy.

Eligibility Criteria:
Inclusion Criteria:

* CKD patients aged 18 to 90 years

Exclusion Criteria:

* no CKD patients, aged below 18 or above 90 years
Influence of Diabetes on Tramadol Pharmacokinetics

This study aimed to investigate the influence of uncontrolled type 1 and type 2 diabetes mellitus (DM) on the kinetic disposition, metabolism and pharmacokinetics-pharmacodynamics of tramadol enantiomers in patients with neuropathic pain. Thus, nondiabetic patients (control group, n = 12), patients with type 1 DM (n = 9), and patients with type 2 DM (n = 9), all with neuropathic pain and phenotyped as extensive metabolizers of cytochrome P450 2D6 (CYP2D6) who were treated with a single oral dose of 100 mg racemic tramadol were investigated.

Tramadol is a centrally acting analgesic that effectively relieves acute and chronic pain, including neuropathic pain in diabetic patients. The drug is available in clinical practice as a mixture of the (+)-tramadol and (-)-tramadol enantiomers. Tramadol is metabolized by CYP2D6 to O-desmethyltramadol (M1) and by cytochrome P450 3A (CYP3A4) and cytochrome P450 2B6 (CYP2B6) to N-desmethyltramadol (M2). Both tramadol enantiomers and (+)-M1 contribute to the analgesic activity of the drug: (+)-tramadol and the (+)-M1 metabolite act as -opioid receptor agonists; (+)-tramadol inhibits serotonin reuptake; and (-)-tramadol inhibits the reuptake of norepinephrine. This study investigated the influence of uncontrolled type 1 and type 2 diabetes mellitus (DM) on the kinetic disposition, metabolism and pharmacokinetics-pharmacodynamics of tramadol enantiomers in patients with neuropathic pain. Nondiabetic patients (control group, n = 12), patients with type 1 DM (n = 9), and patients with type 2 DM (n = 9), all with neuropathic pain and phenotyped as extensive metabolizers of CYP2D6, received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected up to 24 h after administration of the drug for pharmacokinetic study and for the analysis of noradrenaline in plasma. Pain was rated on a visual analog pain scale at the same time as blood sampling. The patients were evaluated for in vivo CYP3A activity using midazolam as a probe drug and genotyped for CYP2B6. Total and unbound plasma concentrations of the tramadol, M1 and M2 enantiomers were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Eligibility Criteria:
Inclusion Criteria:

* Adult patients, both gender
* Patients with self-reported neuropathic pain (score \>4 in a 0-10 visual analog scale)
* Patients with normal renal function (creatinine clearance \>60 mL/min)

Exclusion Criteria:

* Patients with nociceptive somatic pain, visceral or autonomic associated during the study period;
* Patients with morbid obesity (BMI\> 40), congestive heart failure, severe hypertension
* Patients who have had acute myocardial infarction or accident stroke less than 6 months of the period of investigation.
* Patients with chronic obstructive pulmonary disease
* Patients who were in use of analgesics, CYP2D6 inhibitors or CYP3A4 inducers or inhibitors were excluded.
* Pregnant and lactating patients were excluded.
Single Ascending Dose Study in Participants With LCA10

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of EDIT-101 administered via subretinal injection in participants with LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991+1655A\>G in intron 26 of the CEP290 gene ("LCA10-IVS26").

This is an open-label, single ascending dose study of EDIT-101 in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Up to 34 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of EDIT-101 in this study. EDIT-101 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26.

Eligibility Criteria:
Inclusion Criteria:

* Male or female
* At least 3 years of age at screening with CEP290-related retinal degeneration caused by a homozygous or compound heterozygous mutation involving c.2991+1655A\>G in IVS26 of the CEP290 gene.
* Visual Acuity:

  * Sentinel participant will have severe vision loss with a logMAR BCVA of ≥1.6 to 3.9 (20/800 or worse to LP) in the study eye
  * Non-sentinel participants must have BCVA between 1.0 - 3.0 logMAR in the study eye

Exclusion Criteria:

* Other known disease-causing mutations
* Achieves a passing score for the mobility course at the most difficult level
* In either eye, active systemic or ocular/intraocular infection or inflammation
* In either eye, history of steroid-responsive intraocular pressure with increases \> 25 mm Hg following corticosteroid exposure
* Any vaccination/immunization in the last 28 days before screening
* Inability or unwillingness to take oral prednisone
* Prior gene therapy or oligonucleotide treatment
Ultrasound Imaging of Dual Mobility Cup

The concept of dual mobility cup (DMC), developed in the 1970s by Gilles Bousquet, allows a greater motion and a better stability of the implants, reducing the prosthetic dislocations frequency in at-risk populations. This type of prosthesis has a small-diameter head that ensures a low wear rate and a large-diameter head, with a polyethylene liner, to increase prosthetic stability. This prosthesis has survival rates comparable to those found with conventional prostheses. However, actually, its in vivo behaviour has not yet been established, leading orthopaedic surgeons to keep this concept for patients with a high risk of dislocation (elderly subjects, neurological pathologies, spinal pathologies, falls, etc.). To date, no in vivo studies have been carried out - non-invasively and dynamically - to understand the biomechanical behaviour and the stability properties of the dual mobility cup implanted in patients.

The objective of this study is to visualize and quantify the in vivo movement of the polyethylene liner using 3D ultrasound imaging. The second objective is to obtain in vivo data (using the motion analysis system and the force platform) allowing the use of a musculoskeletal model to improve the understanding of the prosthetic dislocation phenomenon.

Participants will carry out daily life activities (walk, chair up, etc.). During this study, liner ultrasound acquisitions and motion analysis of the lower limb will be performed, thanks to a movement analysis system composed of cameras coupled to a force platform.

Hip kinematics will be obtained from the motion analysis data and will be based on the model of Leardini et al. 2007. The position of the liner and liner plane will be determined using 3D ultrasound data. The abduction and anteversion motion of the liner plane will be measured relative to the pelvic landmark.


Eligibility Criteria:
Inclusion Criteria:

* Patient having signed a free and informed consent
* Being affiliated or benefiting from a social security system
* Having dual mobility cup for at least 1 year
* Outside of a period of exclusion from the national file of persons undergoing biomedical research
* Age greater than or equal to 50 years
* Of a cognitive level compatible with oral communication, the respect of instructions and the understanding of the gestures carried out

Exclusion Criteria:

* Persons who are not physically able to perform tests
* Persons currently participating in another research project with an exclusion period
* Persons of full age under legal protection or unable to express their consent
* Pregnant or breast-feeding women (Article L1121-5 of the Public Health Code (CSP))
* Persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care and persons admitted to a health or social institution for purposes other than research
Preoperative Chemo-radiation With IG-IMRT Dose Escalation for Locally Advanced Rectal Cancers

Hypothesis : Therapeutic intensification by increasing the dose delivered to the tumor by RCMI (conformational radiotherapy by intensity modulation) in order to reduce local relapse, often associated with poor prognosis

Primary objective: evaluate the rate of tumor sterilization and the toxicities of RTCT with concomitant boost in intensity modulation in patients with rectal cancer CT3-T4 and / or cN1-2.


Eligibility Criteria:
Inclusion Criteria:

1. Adenocarcinoma of the rectum cT3 or cT4 or cN+, M0 and for which CPR recommends preoperative radiochemotherapy
2. Tumor \<15 cm of the anal margin in rigid or subperitoneal rectoscopy at the MRI
3. Tumor potentially resectable from the outset, or considered to be resectable after radiochemotherapy
4. Operable Patient
5. Age between 18 and 75
6. OMS performance status 0-2
7. No co-morbidity likely to prevent the delivery of treatment
8. Adequate contraception for men, and for non-menopausal women
9. Neurotrophic neutrophils 1500 / mm3, platelets 100 000 / mm3, and hemoglobin 10 g / dL
10. Bilirubin ≤ 1.5 times the upper limit of normal (LNS), ASAT and ALAT ≤ 1.5LNS, Alkaline phosphatase ≤ 1.5 LNS
11. Creatinine clearance\> 50 mL / min
12. Patient must have been informed and must have signed the specific informed consent form.
13. Patient must be affiliated to a Social Health Insurance.

Exclusion Criteria:

1. Remote metastasis
2. Cancer not resectable
3. Contraindication to capecitabine and its excipients
4. Previous history of pelvic radiotherapy or previous chemotherapy
5. History of inflammatory bowel or rectum disease
6. History of angina pectoris monitored or myocardial infarction or heart failure
7. Active active infection or other serious underlying condition that may prevent the patient from receiving treatment
8. Other concomitant cancer, or history of cancer other than in situ cancer of the treated cervix or basal cell carcinoma or squamous cell carcinoma
9. Patient already included in another therapeutic trial with an experimental molecule
10. Pregnant woman, likely to be pregnant or nursing
11. Persons deprived of their liberty or under guardianship
12. Patient unable to comply with the required medical follow-up for geographic, social or psychological reasons
Non Invasive Ventilation (NIV) Related Practices, Monitoring of the NIV Treatment Effect and of the Patient's Comfort

The practices and processes related to the administration of noninvasive ventilation (NIV) in the adult intensive care unit (ICU) of the University hospital of Lausanne will be recorded by an investigator at the bedside. The effect of the NIV treatment on various respiratory parameters ( respiratory rate, expired tidal volume, minute ventilation) will also be recorded using a pneumotachograph. Finally patient's comfort during NIV treatment will be evaluated.


Eligibility Criteria:
Inclusion Criteria:

* Respiratory failure
* Therapeutic treatment by NIV required

Exclusion Criteria:

* Age \< 18 years old
* Prophylactic NIV treatment
* Continuous Positive Airway Pressure (CPAP)treatment
* Denied consent
CARE Mentalizing-Focused Parenting Group Outcomes Study

The primary objective of this clinical trial is to evaluate the 12-week mentalizing-focused group parenting intervention, Connecting and Reflecting Experience (CARE), relative to a treatment as usual (TAU) group in an outpatient child mental health clinic.


Eligibility Criteria:
Inclusion Criteria:

* Parents/caregivers of child receiving mental health services at community child outpatient clinic
* English- or Spanish-speaking

Exclusion Criteria:

* Parent has severe mental illness or significant cognitive impairment
* Child has significant developmental delay
A fMRI Study of Compressive Spinal Cord

Cervical myelopathy (CM), a chronically compressive spinal cord lesion, is the most common cause of non-traumatic paraparesis/quadriparesis among the elderly. Hong Kong is facing a heavy social economic burden from CM with the rapidly aging population. Surgical decompression is considered as the mainstay of the treatment for CM patients to relieve their symptoms and signs. Yet the surgical outcome is not always satisfactory. There is a pressing need for understanding the exact mechanism of surgical decompression on the recovery of myelopathic cord in order to improve the prognosis of CM patients in near future.This project will evaluate neuronal activities and axon regeneration by longitudinally monitoring at time zero, 3 and 6 month after the surgery in CM patients using UTE, BOLD-fMRI and DTI, and to investigate the relationship of preoperative neuronal activities of myelopathic cord with axon regeneration.

This study aims to monitor the structural and functional changes of chronically compressed spinal cords longitudinally after surgical decompression in vivo. Three kinds of MRI techniques will be used in this study. These are (1) axial T1-weighted (T1WI) and T2-weighted imaging (T2WI), UTE MRI, (2) BOLD-based fMRI, and (3) diffusion tensor imaging (DTI). To quantitatively investigate the structural deficits, T1/T2 MRIs will delineate the gross morphology of the spinal cord, CSF, and surrounding anatomical structures, while DTI will quantify the fiber orientation and integrity within the spinal cord. BOLD-based functional MRIs will assess the local hemodynamic changes and neuron activities in response to the motor or sensory stimulation along the C3 to C8 spinal nerve levels. The MRI evaluations will be applied to the same cervical myelopathy (CM) patient before surgery and 3 and 6 months post-surgery, when clinical recovery reaches a plateau9. Clinical examination will include neurological evaluation, Japanese Orthopaedic Association (JOA) scoring assessment, and clinical electrophysiological evaluation.

Eligibility Criteria:
Inclusion Criteria:

* The inclusion criteria are a clinical diagnosis of CM including the signs of corticospinal lesion/s together with the appropriate radiographic findings.

Exclusion Criteria:

* Patients with acute spinal cord injuries, prior spinal intervention or claustrophobia will be excluded.