cyrilzakka/clinical-trials huggingface dataset:
Dose-determining and Dose-confirmatory Study to Investigate the Optimal Dose of Tamoxifen in Breast Cancer Patients According to Genotype Status of TCF20 rs932376

The investigators hypothesize that the TCF20 rs932376 locus controls endoxifen levels in estrogen receptor (ER)-positive breast cancer patients on tamoxifen therapy and that the requirement of tamoxifen dose to achieve therapeutic levels of endoxifen varies according to the genotype status of the patient's at the TCF20 rs932376 locus.

Patients will receive escalating doses of tamoxifen according to their TCF20 rs932376 genotype status. Patients on 20mg tamoxifen daily for 8 weeks or longer will provide blood samples for analysis of tamoxifen and its metabolites. Patients assess with \>30nM endoxifen concentrations will continue with 20mg tamoxifen dose. Patients who have endoxifen concentrations \<30nM will receive dose increments of 10mg every 8 weeks until they achieve endoxifen threshold of \>30nM or reach maximum dose level of 40mg/day.


Eligibility Criteria:
Inclusion Criteria:

* Histologically or cytologically confirmed stage I to IV breast cancer
* Age greater than 21 years
* Estrogen- or progesterone-receptor positive tumours
* Patients receiving tamoxifen 20mg daily as monotherapy
* Patients currently taking tamoxifen in either adjuvant or metastatic setting for greater than or equal to 8 weeks (for Dose determination and confirmation phases)
* Patients who will commence on tamoxifen therapy in either adjuvant or metastatic setting (for Dose confirmation phase only)
* Written and informed consent from participating patients

Exclusion Criteria:

* Patients with expected survival less than 6 months
* Patients who are human epidermal growth factor receptor 2 (HER2)-postitive
* Inability to provide informed consent
* Patients receiving CYP2D6 inhibitors or inducers within the past four weeks from the time of study enrollment. However, patients started in CYP2D6 inhibitors or inducers after commencing on tamoxifen therapy will not be excluded from the study.
* Pregnancy
* Patients with prior malignancies other than those who have received curative treatment for basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements.
* Patients who have documented prior allergic reaction to tamoxifen
Myocene Sensivity to Cycling Intensities

This study aims to address this gap by assessing LFF following different efforts in cycling, aiming to identify a pattern. Also, we expect that this study helps to clarify to which efforts (prolonged vs short) are more likely to trigger substantial changes in LFF responses.


Eligibility Criteria:
Inclusion Criteria:

* Road cyclists

Exclusion Criteria:

* Injured or recently injured participants
Optimization Post-TAVR to IMprove Activity Levels (OPTIMAL Study)

In this study, the investigators will evaluate the feasibility and potential efficacy of programs to improve functional outcomes after minimally-invasive transcatheter aortic valve replacement (TAVR). The investigators will examine the potential efficacy of (a) a motivation interviewing program, and (b) a home-based physical activity + motivational interviewing program, compared to (c) usual care + enhanced education in patients post-TAVR procedure.


Eligibility Criteria:
Inclusion Criteria:

* Undergoing TAVR procedure
* ≥65 years old
* Ambulatory at baseline without assistance
* Approval of the interventional cardiologist that the patient is an appropriate candidate
* Can access telephone or teleconference

Exclusion Criteria:

* Impaired cognition that would limit participation in study activities
* Medical comorbidities that substantially limit exercise
* Major cardiac comorbidities, including ejection fraction\<35%, history of cardiac arrest, complex dysrhythmias at rest, clinically-significant incomplete revascularization, implanted cardiac defibrillator.
* Physical characteristics that substantially limit exercise
* High fall risk (Johns Hopkins Fall Risk Assessment Tool indicating high risk)
* Non-English Speaking
* Vigorous exercise at least 2 times/week for \>30 minutes
* Any other physician judgement
A Phase 1 Study of S-1117

This is the first-in-human study of S-1117 designed to provide safety, tolerability, pharmacokinetic, and pharmacodynamic data in healthy volunteers.

This is a randomized, placebo-controlled, double-blind, study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of S-1117 administered to healthy adult participants. This study will be conducted in two parts, Part 1 (single ascending dose, SAD) and Part 2 (multiple ascending doses, MAD).

Eligibility Criteria:
Major Inclusion Criteria:

1. Is available for the entire duration of the study and follow up.
2. Is willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
3. Voluntarily consents to participation in the trial as documented by signing the study informed consent form (ICF).
4. Has a body mass index (BMI) within 18 to 32 kg/m2, inclusive, and weighs ≥45 kg.
5. Is in good physical and mental health in the opinion of the Investigator or delegate.

Major Exclusion Criteria:

1. Has a history of severe allergic or anaphylactic reaction as determined by the Investigator or delegate.
2. Is pregnant, nursing, or is planning to become pregnant or breastfeed during the trial.
3. Has a known immunodeficiency disorder.
4. Has a history of malignancy other than non-melanoma skin cancer.
5. Has a history of human immunodeficiency virus (HIV) or positive serology for HIV at Screening.
6. Has positive laboratory evidence for active hepatitis at screening.
7. Has received a live vaccine within 2 months of Screening.
8. Has any other condition or prior therapy that, in the opinion of the Investigator or delegate, may potentially compromise the safety or compliance of the participant, or may preclude the participant from successfully completing the study.

Other inclusion/exclusion eligibility criteria apply.
A Dose Escalating Clinical Trial of the IGF-1 Receptor Inhibitor AXL1717 in Patients With Advanced Cancer

A dose escalating phase Ia-b clinical trial of the IGF-1 receptor inhibitor AXL1717 in patients with advanced cancer.

The objective is to study the safety and pharmacokinetics of AXL1717 and to define an appropriate Phase 2 dose for further studies. This is the first study in man. The study is not designed to show tumor response.


Eligibility Criteria:
Inclusion Criteria:

1. At least 18 years of age.
2. Histologically confirmed diagnosis of advanced solid or haematological malignancy not amenable to standard treatment.
3. Pharmacological treatment attempt justified
4. Preserved major organ functions, i.e:

   * B-Leukocyte count ≥ 3.0 x 109/L
   * B-Neutrophil count ≥ 1.5 x 109/L
   * B-Platelet count ≥ 75 x109/L
   * B-Haemoglobin ≥ 100 g/L (transfusions are allowed)
   * P-Total bilirubin level ≤ 1.5 times the upper institutional limit of the "normal" (i.e. reference) range
   * P-ASAT or P-ALAT ≤ 2.5 times upper institutional limit of the "normal" range, ≤5 times if liver metastases have been documented
   * P-Creatinine ≤ 1.5 times upper institutional limit of the "normal" range
5. Females of childbearing potential should use adequate contraception (oral or injectable contraceptives, hormone releasing intrauterine device) throughout the study period.
6. Signed written informed consent.

Exclusion Criteria:

1. Ongoing infection or other major recent or ongoing disease that, according to the investigator, poses an unacceptable risk to the patient
2. Known malignancy in CNS
3. Prior anti-tumour therapy within 4 weeks from enrolment (6 weeks for nitrosurea and MitC).
4. Pregnancy or lactation
5. Current participation in any other interventional clinical trial
6. Performance status \> ECOG 2 after optimization of analgesics
7. Life expectancy less than 3 months
8. Contraindications to the investigational product, e.g. known or suspected hypersensitivity.
9. Lack of suitability for participation in the trial, for any reason, as judged by the Investigator.
Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With High Risk Coronary Artery Disease (FORWARD)

The primary objective was to evaluate the effect of treatment with evolocumab on the risk for cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, whichever occurs first, in patients with high risk coronary artery disease.


Eligibility Criteria:
Inclusion Criteria:

* Male or female ≥ 18 years of age
* Coronary artery disease at high risk (Syntax Score ≥ 33)
* Patients had to have a fasting LDL cholesterol level of 1.4 mmol per liter while they had been taken an optimized regimen of lipid-lowering therapy for at least 4 weeks, which was defined as preferably a high intensity statin but must have been at least atorvastatin at a dose of 20 mg daily or its equivalent, with or without ezetimibe.

Exclusion Criteria:

* New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction \< 30%
* Uncontrolled hypertension
* Uncontrolled or recurrent ventricular tachycardia
* Untreated hyperthyroidism or hypothyroidism
* Homozygous familial hypercholesterolemia
* LDL or plasma apheresis
Apatinib Versus Placebo as a Third Line Treatment in Patients With Advanced or Metastatic Gastric Cancer

Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable and the maximum tolerable daily dose is 850 mg. The purpose of this study is to determine whether apatinib can improve progression free survival compared with placebo in patients with metastatic gastric carcinoma who failed two lines of chemotherapy.

Up to now, although FU based, cisplatin based and taxane based regimen, and ECF regimen have been suggested as the first line therapy for A/MGC by FDA, the efficacy of these treatment is still unsatisfied for their toxicity and limitation in prolonging survival. Based on the promising results of apatinib in the phase I study, this clinical trial has been designed to evaluate whether apatinib can improve progression free survival in patients with metastatic gastric carcinoma who failed two lines of chemotherapy compared with placebo. Patients will be randomized to 3 groups, one group patients will receive the treatment of apatinib 850mg qd, one group patients will receive apatinib 425mg bid, and the other group will receive placebo.

Eligibility Criteria:
Inclusion Criteria:

* ≥ 18 and ≤ 70 years of age
* Histologically confirmed advanced or metastatic adenocarcinoma of the stomach
* Have failed for 2 lines of chemotherapy
* Life expectancy of more than 3 months
* ECOG performance scale ≤ 2
* At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
* Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
* More than 4 weeks for operation or radiotherapy
* More than 4 weeks for cytotoxic agents or growth inhibitors
* Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 109/L, neutrophil \> 2.0 × 109/L, serum creatinine ≤ 1.5mg/dl, total bilirubin within upper limit of normal(ULN), and serum transaminase≤2.5×the ULN).

Exclusion Criteria:

* Pregnant or lactating women
* History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Any factors that influence the usage of oral administration; Evidence of CNS metastasis
* History of another malignancy within the last five years except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Intercurrence with one of the following: hypertension, coronary artery disease, arrhythmia and heart failure
* Receiving the therapy of thrombolysis or anticoagulation
* Abuse of alcohol or drugs
* Allergy to the ingredient of the agent or more than two kinds of food and drug
* Less than 4 weeks from the last clinical trial
* Disability of serious uncontrolled intercurrence infection.
Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)

This study will determine the advantages and disadvantages of adding one of two different types of drugs to stimulant treatment for reducing aggressive behavior in children with attention deficit with hyperactivity disorder (ADHD).

Attention deficit with hyperactivity disorder (ADHD) is a common childhood mental disorder that affects 3% to 5% of all American children. Symptoms of ADHD commonly include inability to focus or exercise normal inhibition, and in some cases, aggressive behavior. Approximately 33% to 50% of children with ADHD develop oppositional defiant disorder (ODD), and about 20% to 40% develop a conduct disorder (CD). These disorders are characterized by defiant, belligerent, and otherwise aggressive behavior. Treatment for ADHD generally includes use of stimulant medications that decrease impulsivity and increase attentiveness, such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine), but these do not always affect aggression. To treat aggression in ADHD, many physicians prescribe additional medications, including the mood stabilizing medication valproate and the antipsychotic medication risperidone.

There is no clinical evidence proving that using multiple types of medications is safe and effective. This study will treat children with ADHD and aggression with a combination of stimulants and antipsychotic or mood stabilizing medications to determine whether the aggressive behaviors and ADHD symptoms are reduced without harmful side effects.

This study has two phases. During the first phase, which will last 3 to 6 weeks, participants will be treated with normal ADHD stimulant medications. During the second phase, those whose aggressive behavior is not effectively suppressed by stimulant medication alone will then be randomly assigned to also receive valproate, risperidone, or placebo for 8 weeks. After 8 weeks, children whose aggression persists will be switched from either valproate to risperidone or risperidone to valproate for another 8 weeks. Those on placebo will not switch medications. All participants will attend weekly monitoring visits for 11 to 16 weeks over the course of the study. At these visits, aggression levels and medication side effects will be assessed. Families will also meet with the researchers to discuss the child's progress and will attend behavioral counseling with a therapist.

Eligibility Criteria:
Inclusion Criteria:

* Presence of ADHD
* Presence of persistent, clinically significant aggression
* Presence of ODD or CD

Exclusion Criteria:

* Presence of psychosis
* Presence of a major developmental disability
* Presence of a major mood disorder
* Contraindications to stimulant, valproate, or risperidone treatment
The Efficacy and Safety Study of High Dose Donepezil in Parkinson's Disease With Dementia

The purpose of this study to evaluate the safety and efficacy of high-dose donepezil (23mg) in Parkinson's disease with dementia compared to standard dose donepezil.

This study is open-label, prospective, randomized paralleled study. The investigators evaluate the efficacy of high-dose donepezil in patients with Parkinson's disease with dementia (PDD) who have taken standard donepezil (10mg) for 12 weeks. The participants, who sign the informed consent, are assigned into two groups randomly (high-dose donepezil group and standard donepezil group). All participants will be maintained the medication for 24 weeks and assessed cognitive function at 24 weeks. They will visit to clinic for 3 times (4, 12, 24 weeks) to assess cognitive function and adverse event. After the end of study, all participants were administrated by standard dose donepezil again.

Eligibility Criteria:
Inclusion criteria :

* Patients diagnosed as Parkinson's disease according to Queen Brain Bank criteria
* Patients who have been diagnosed as dementia after diagnosing Parkinson's disease at least 1 year.
* Patients with Hoehn and Yahr staging from 2 to 4
* Patients with MMSE score from 10 to 24
* Patients who have taken donepezil for at least 12 weeks before screening period
* Patients whose medications for Parkinson's disease have not change for 1 month
* Patients who give informed consent

Exclusion criteria :

* Patients who cannot be performed neuropsychiatric test because of hearing and visual difficulty
* Patients who have taken medicine affecting cognitive function such as anticholinergic drug and memantine -Patients diagnosed as dementia with Lewy body and vascular dementia-
* Patients who have history of neurosyphilis, head trauma, encephalitis or other movement disorders
* Patients who have psychiatric disease
* Except patients who are stable state under antidepressant or atypical neuroleptics
* Patients with child-bearing periods
* Patients who have severe liver or kidney disease necessary for aggressive treatment
* Patients who have gastrointestinal disease needed for treatment
* Patients who cannot taken tablet per oral
* Patients who are participated in other clinical trial except observational study
Carotid Revascularization With ev3 Arterial Technology Evolution (CREATE) Trial

Evaluate the safety and efficacy of the Protege Stent and Spider Device in the treatment of common and/or internal carotid artery stenoses for subjects that are high risk for carotid endarterectomy.


Eligibility Criteria:
Inclusion Criteria:

* 18 years and above
* informed consent
* for female subjects, not pregnant or planning on becoming pregnant
* meet protocol defined anatomical or clinical high risk criteria

Exclusion Criteria:

* participation in another clincial study which may affect either the pre-procedure or follow-up results
* prior stenting of the ipsilateral carotid artery
* life expectancy less than twelve months
* known allergy or intolerance of study medications or device materials
* must not meet general or angiographic exclusion criteria as defined in the protocol
A Novel Combinatory Approach to Maximize Functional Recovery of Learning and Memory in Multiple Sclerosis

The goal of this novel study is to compare the effect of a combined cognitive rehabilitation and exercise approach on new learning and memory (NLM) in persons with multiple sclerosis (pwMS) and mobility disability.

The proposed research study will be the first to apply the Kessler Foundation modified Story Memory Technique (KF-mSMT®), the practice standard for cognitive rehabilitation, with one of two exercise programs. Alone, KF-mSMT® has been beneficial to NLM impairment, however, its effects are highly selective to list learning and as such, will not maximally restore NLM function. The combination of KF-mSMT® and exercise provides a robust approach towards maximal functional recovery.

Eligibility Criteria:
Inclusion Criteria:

* Be within the ages of 18 and 70 years of age
* Speak English as their primary language
* Confirmed MS diagnosis by a neurologist
* Be relapse and steroid-free for at least 30 days
* Mild-to-moderate self-reported mobility disability, based on the Patient Determined Disease Steps scale (PDDS)
* Currently physically inactive, based on the Godin Leisure Time Exercise Questionnaire (GLTEQ)
* Right handedness

Exclusion Criteria:

* History of neurological disorders besides MS or history of uncontrolled psychiatric disorders (ex: major depression)
* Have contraindications to exercise, based on the Physical Activity Readiness Questionnaire (PAR-Q)
* Currently use medications that may impact cognition (ex: steroids, benzodiazepines)
* Currently pregnant
* Contraindication for MRI (metal or electronic devices in the body that are not considered MRI safe)
* Severe cognitive impairment as measured by the Modified Telephone Interview of Cognitive Status (TICS-M)
A Study of the Safety of Oral Elsubrutinib Capsules and Oral Upadacitinib Tablets Given Alone or in Combination (ABBV-599) for Adult Participants With Moderately to Severely Active Systemic Lupus Erythematosus to Assess Change in Disease State

Systemic Lupus Erythematosus (SLE) is an immune-mediated disease associated with inflammation of multiple organ systems. This study will evaluate how well elsubrutinib and upadacitinib given alone or as the ABBV-599 combination (elsubrutinib/upadacitinib) works within the body, in participants who completed study M19-130. This study will assess the change in disease symptoms.

ABBV-599 is an investigational drug being developed for the treatment of Systemic Lupus Erythematosus (SLE). This study is "double-blinded", which means that neither the trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants into 1 of 4 groups called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of SLE will be enrolled. Around 260 participants will be enrolled in the study in approximately 100 sites worldwide.

Participants will receive the following for up to 56 weeks:

Participants will receive oral elsubrutinib capsules and/or oral upadacitinib tablets once daily for up to 56 weeks. Participants who were receiving elsubrutinib and/or upadacitnib in M19-130 will continue to receive the same treatment in this study. Participants who were receiving placebo in M19-130 will be re-randomized to one of the 2 combination treatment arms in this study.

Arm 1: Elsubrutinib Dose A and Upadacitinib Dose A Arm 2: Elsubrutinib Dose A and Upadacitinib Dose B

There may be higher burden for participants in this trial compared to their standard of care. Participants will attend monthly visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility Criteria:
Inclusion Criteria:

* Completed Study M19-130 (i.e., the randomized controlled trial of elsubrutinib, upadacitinib, and ABBV-599 \[elsubrutinib/upadacitinib\] combination or matching placebo) and will not have developed any laboratory or clinical discontinuation criteria as defined in that study.
* On stable background treatment for SLE throughout the study.

Exclusion Criteria:

* Active, chronic, or recurrent viral, or bacterial infection.
* Active tuberculosis (TB)
* History of gastrointestinal (GI) perforation, diverticulitis, or a significantly increased risk for GI perforation per investigator assessment.
* Participant require vaccination with live vaccine during study participation.