Clinical trials

Major depressive disorder (MDD) often involves cognitive deficits, particularly in cognitive flexibility, which is inadequately addressed by standard antidepressants. This study tests an innovative brain stimulation regimen: individualized dual-target repetitive transcranial magnetic stimulation (rTMS) to improve cognitive flexibility in MDD patients. This is a randomized, double-blind, sham-controlled trial that plans to enroll 105 MDD patients with cognitive flexibility impairment. Participants will be randomly assigned to one of three groups: (1) Active dual-target group - receiving active rTMS over both the left inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (DLPFC); (2) Active single-target group - receiving active rTMS over the left IPL and sham stimulation over the right DLPFC; (3) Sham control group - receiving sham stimulation over both targets. All participants will continue their stable antidepressant medication (SSRI or SNRI). The rTMS intervention lasts 10 days, with 5 stimulation sessions per day. Cognitive flexibility, depressive symptoms, and brain functional connectivity will be assessed at baseline, immediately after the 10-day treatment, and at 2-week and 4-week follow-ups using neurocognitive tests, clinical rating scales (e.g., HAMD), and functional MRI. The results will help confirm the role of the IPL-DLPFC connectivity in cognitive flexibility and may establish a new treatment target for cognitive dysfunction in MDD.

The goal of this randomized, double-blind, placebo-controlled clinical trial with an open-label extension is to evaluate whether sulforaphane can improve negative symptoms and cognitive impairment, and to explore its underlying mechanisms in patients with schizophrenia (aged 12-45 years, both sexes, stable on antipsychotic medication). The study duration includes 12 weeks of double-blind treatment followed by a 12-week open-label extension. In the randomized controlled double-blind phase, a total of 60 participants will be randomized 1:1 to receive either six oral tablets (411 μmol GR) of sulforaphane (SFN group, n = 30) or placebo (placebo group, n = 30) for 12 weeks. In the open-label phase, participants will choose whether to continue taking the drugs originally assigned. The primary outcome is the change in PANSS and BNSS scores during the randomized double-blind phase. Secondary outcomes include changes in brain MRI measures, as well as changes in MCCB, CGI-SI, CGI-GI, PSP, SNS, and SAFTEE scores during the randomized double-blind phase; and changes in PANSS, BNSS, and MCCB scores during the open-label phase.SAFTEE scale, serious adverse event record and blood test will be used for safety monitoring.

The goal of this observational study is to evaluate the predictive value of the genetic risk score for type 1 diabetes in the progression to insulin deficiency in diabetic patients. The main question it aims to answer is: 1. To investigate the predictive efficacy of the genetic risk score for T1DM in determining whether diabetic patients will progress to insulin deficiency; 2. To compare the differences in genetic characteristics between the insulin-deficient cohort and the non-insulin-deficient cohort. This study is a nested case-control study, in which a case group and a control group are set up for the collection of observational indicators. Case group: Diabetic patients who "progressed to insulin deficiency" and those who "progressed to severe insulin deficiency". Control group: Patients who did not progress to insulin deficiency. The study period is 3 years.

The value of intelligent lifestyle intervention for T2D and its complications has been initially explored, but evidence-based support for the effectiveness of related AI risk prediction models and intervention models remains to be confirmed. The primary objective of this study is to verify the effectiveness of an AI model for predicting the risk of T2D complications based on phenotype, laboratory indicators and wearable device indicators, and to explore the effect and applicability of an intelligent lifestyle intervention model combining wearable devices and smartphones in preventing T2D complications.

This single-center, randomized, open-label, controlled study aims to evaluate the effect of cofrogliptin on pancreatic β-cell function in adults with latent autoimmune diabetes in adults (LADA). Following a screening period of up to 6 weeks, 84 eligible participants will be randomized in a 1:1 ratio via a sealed-envelope method, stratified by baseline GADA titer (≥0.3 vs \<0.3). Participants will be assigned to one of two treatment arms: (1) metformin (with or without insulin) plus vitamin D3, or (2) metformin (with or without insulin) plus vitamin D3 and cofrogliptin. Cofrogliptin will be administered orally at a dose of 10 mg once every 2 weeks, and vitamin D3 at 2000 IU once daily, for a total treatment duration of 52 weeks. Study visits are planned at baseline and at Weeks 12, 26, 38, and 52, during which mixed-meal tolerance tests (MMTT) and other protocol-specified assessments will be conducted.

The purpose of this pilot study is to evaluate the feasibility, acceptability, and preliminary effects of an Acceptance and Commitment Therapy (ACT)-based psychosocial intervention for women who have experienced perinatal loss (miscarriage, stillbirth, or neonatal death). The intervention is a 4-week programme delivered in a mixed format: four in-person sessions (hospital setting, one-on-two with spouse/significant other) and two videoconferencing sessions (post-discharge, one-on-one), plus a 30-minute booster session one month after completion. Outcome assessments will occur at baseline (pre-intervention), immediately post-intervention, and three months post-intervention. Primary feasibility and acceptability metrics include recruitment, retention, session attendance, and participant-rated satisfaction. Preliminary effectiveness outcomes include perinatal grief, post-traumatic stress, depression, anxiety, psychological flexibility, and perceived social support. A qualitative component (semi-structured interviews) will explore participants' experiences and suggestions for refinement.

Cervical cancer, ranking as the fourth most prevalent malignancy in women globally, presents significant challenges in nutritional management. Approximately 31% of patients develop cancer-related malnutrition/cachexia, with 10-20% of deaths directly attributable to nutritional depletion. The disease process and its treatment - particularly concurrent chemoradiotherapy (CCRT) - create a destructive cycle through multiple mechanisms. Tumor-derived factors (including activins and myostatin) and inflammatory cytokines (such as TNF-α and IL-6) actively promote muscle and fat catabolism. CCRT toxicity, especially from platinum-based drugs, worsens this condition by inducing mitochondrial dysfunction and accelerating protein degradation, leading to clinically significant sarcopenia. This metabolic disruption has dire consequences, with studies showing severe weight loss during CCRT correlating with a 2.37-fold increase in mortality risk (HR 2.37, p=0.036). Nanocrystalline megestrol acetate (MA) emerges as a promising therapeutic intervention with dual mechanisms of action. Centrally, it modulates D2 receptors to upregulate neuropeptide Y (NPY), effectively stimulating appetite. Peripherally, it suppresses key inflammatory cytokines (IL-6 and TNF-α), thereby reducing systemic inflammation and muscle wasting. Its efficacy is well-established, with endorsement from major oncology guidelines (ASCO, NCCN, ESMO) for cancer cachexia management. A comprehensive meta-analysis of 35 clinical trials involving 4,234 patients demonstrated MA's superiority over placebo, showing significant improvements in appetite (RR 2.2), weight gain (RR 1.6), and quality of life (RR 1.8). The nanocrystalline formulation represents a substantial pharmacological advancement over conventional MA. While traditional preparations have limited solubility (2 µg/mL) and require high-fat meals for adequate absorption, the nanocrystalline version (with particles reduced to 26.6 nm) demonstrates 22% greater bioavailability. This translates to clinically meaningful differences: fasting-state peak concentrations increase from 187 ng/mL to 1,133 ng/mL, the time to observable effect shortens from 14 days to just 3 days, and 12-week weight gain improves from 3.5 kg to 5.4 kg (with 40% being lean mass). Dose optimization studies confirm 800 mg/day as the optimal conventional MA dose, with the nanocrystalline equivalent being 625 mg/day due to its enhanced bioavailability. The proposed clinical investigation will evaluate this intervention in FIGO IB3-IVA cervical cancer patients (n=5) undergoing CCRT. The study employs a two-arm design comparing nanocrystalline MA (625 mg/day) plus CCRT against CCRT alone. Primary endpoints focus on BMI changes at 8 weeks, with secondary assessments of nutritional status, inflammatory markers, and quality of life measures. This research aims to establish nanocrystalline MA as a means to break the cachexia cycle in cervical cancer treatment, potentially improving both treatment tolerance and survival outcomes.

The aim of the China Diabetes Type 1 Study (CD1S) is to conduct a nationwide type 1 diabetes (T1D) registry study in patients with T1D and in pediatric adolescent patients with diabetes who had an age of onset \<= 20 years. CD1S compromises a retrospective study enrolling inpatients hospitalized from Jan 1st, 2016 to Dec 31, 2021, and a prospective study beginning from the year 2022.

This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of Chiglitazar Sodium combined with lifestyle intervention for reversing prediabetes to normal glucose metabolism. Eligible participants with prediabetes will be randomized 1:1 to receive either Chiglitazar Sodium 48 mg once daily or matching placebo, both combined with standardized lifestyle intervention, for 52 weeks, followed by a 12-week observation period and optional long-term extension. The primary endpoint is the reversion rate to normal glucose metabolism at week 64. Secondary endpoints include progression to type 2 diabetes, glycemic control, lipid profile, blood pressure, UACR, HOMA-IR, HOMA-β, body weight, BMI, and waist-to-height ratio. Exploratory endpoints include inflammatory markers and long-term cardiovascular outcomes. Safety endpoints include adverse events, vital signs, ECG, and laboratory parameters.

The purpose of the proposed pilot randomized controlled design study is to evaluate the feasibility, acceptability, and potential effectiveness of using a videoconferencing-based individual Acceptance and Commitment Therapy (ACT) approach to enhance the mental well-being and parenting competence of parents of children with hearing loss post-cochlear implantation over a three-month period after the intervention has taken place.

The CR1STAL-Adaptive study is a randomized, open-label, phase II multicenter interventional trial designed to evaluate the safety and efficacy of Ivonescimab (PD-1/VEGF bispecific antibody) combined with docetaxel versus standard treatment in patients with advanced NSCLC who have achieved long-term benefit from first-line immune checkpoint inhibitors (ICIs), but are ctDNA-MRD positive. Building upon insights from previous CR1STAL study (NCT05198154), the CR1STAL-Adaptive study supports the development of precision-guided, adaptive treatment strategies to delay progression and improve outcomes in NSCLC patients with a long-term response to immunotherapy. It represents a step forward in integrating dynamic molecular monitoring with individualized intervention strategies in the era of immunotherapy.

The purpose of this study is to investigate the therapeutic effect and safety of Sorafenib in T1DM patients.

This investigator-initiated, single-center prospective study is designed to clarify how patent foramen ovale (PFO) relates to brain function abnormalities in patients with drug-refractory migraine with aura (MA), and whether percutaneous PFO closure is associated with measurable, longitudinal improvements in neurophysiological and neuroimaging markers as well as clinical symptoms. The study addresses two core questions: (1) Do MA patients with clinically significant right-to-left shunt due to PFO demonstrate distinct resting-state brain function patterns-captured by high-density EEG (hdEEG), resting-state functional MRI (rs-fMRI), and standardized cognitive testing-compared with MA patients without PFO? (2) In MA patients with PFO who undergo clinically indicated percutaneous PFO closure, do these multimodal brain function measures change over time after closure (pre-procedure vs 1, 6, and 12 months), and are such changes accompanied by improvement in migraine burden, quality of life, and mood/anxiety symptoms? The protocol includes two phases. In Phase 1 (cross-sectional comparison), two groups are evaluated at baseline: MA with PFO (PFO+/MA+) and MA without PFO (PFO-/MA+). Participants complete hdEEG and rs-fMRI to characterize whole-brain power spectral density and connectivity, and undergo MATRICS Consensus Cognitive Battery (MCCB) testing and validated symptom/psychological assessments (e.g., MIDAS, MSQ v2.1, PHQ-9, GAD-7, RoPE). In Phase 2 (prospective self-controlled cohort), eligible PFO+/MA+ participants who proceed to percutaneous PFO closure as part of routine clinical care are followed longitudinally with repeated multimodal assessments at pre-closure baseline and post-closure 1, 6, and 12 months. This phase evaluates within-person trajectories of resting-state brain function (hdEEG, rs-fMRI) and cognition/emotion measures, together with migraine diary-based outcomes and patient-reported quality of life/disability and mood/anxiety scales. Key eligibility focuses on adults aged 18-65 years with ICHD-3-defined migraine with aura and a history of frequent migraine (≥4 migraine days/month during screening) despite prior preventive therapy trials; the PFO group requires echocardiographic confirmation of PFO with at least moderate right-to-left shunt (e.g., during Valsalva on contrast TEE), consistent with the study's focus on clinically meaningful shunt physiology. The primary endpoints are multimodal brain function and cognition measures. In Phase 1, the main outcomes include between-group differences in MCCB composite score, rs-fMRI whole-brain functional connectivity strength, and hdEEG spectral power across frequency bands (delta/theta/alpha/beta/gamma) and theta-band connectivity quantified by whole-brain phase-lag index (PLI). In Phase 2, the primary outcome is the 12-month post-closure change in these multimodal resting-state brain function measures, reflecting dynamic neural recovery or reorganization after PFO closure. Secondary outcomes include changes in migraine clinical metrics (monthly migraine days, attack frequency and duration, and complete remission rate), migraine-specific quality of life (MSQ v2.1), disability (MIDAS), and depression/anxiety symptom scores (PHQ-9 and GAD-7) over follow-up. Safety outcomes include adverse events potentially related to the closure procedure and routine post-procedural anti-thrombotic therapy, captured throughout follow-up.

The goal of this observational study is to develop and validate a machine learning-based model for predicting pain recurrence risk after percutaneous balloon compression (PBC) in adult patients with primary trigeminal neuralgia (TN) who had their first PBC treatment. The main questions it aims to answer are: Can the machine learning-based model accurately predict pain recurrence after PBC in these primary TN patients? What key factors (like patient baseline traits, imaging parameters, surgical operation data) affect PBC post-operative pain recurrence? Do machine learning algorithms perform better than traditional Cox proportional hazards regression in predicting such recurrence? Participants (with existing PBC treatment records) will have their past data-including clinical info from the hospital's electronic medical record system, imaging data from the image archiving system, surgical data from the surgical anesthesia system, and follow-up data from the outpatient system-collected and analyzed to build and validate the prediction model.

The purpose of this observational study is to investigate the predictive power of pulse pressure variability during forced inhalation（PPVfi） on the occurrence of hypotension in elderly patients after induction of general anesthesia. The main question it aims to answer is: Can the PPVfi predict the occurrence of hypotension in elderly patients after induction of general anesthesia? By recording the PPV of patients during forced inhalation before anesthesia induction, with the incidence of hypotension as the state variable and PPV as the test variable, the area under the ROC curve was calculated to determine the optimal threshold, sensitivity, and specificity of PPV.

The GLITTER Study 2 is a cluster randomized trial that will evaluate the impact of comprehensive and intensive management, comprising a team, technology, education, and peer resources, on metabolic control and psychological outcomes in patients with type 1 diabetes.

To explore the safety and efficacy of attapulgite in the treatment of obese individuals or overweight/obese individuals with type 2 diabetes.

Glycemic control in surgical patients with type 2 diabetes mellitus (T2DM) receiving parenteral nutrition represents a major clinical challenge. This randomized controlled trial evaluates the comparative effectiveness and safety of hybrid closed-loop (HCL) insulin delivery versus conventional insulin pumps combined with continuous glucose monitoring (CGM) in perioperative T2DM patients requiring short-term parenteral nutrition.

This study was designed to investigate the safety and efficacy of CM355 in patients with refractory SLE.

The GLITTER study is comprised of four key components: Team, Technology, Education, and Peer Resources. The aim of the GLITTER Study is to improve the metabolic control rate in patients with type 1 diabetes through a comprehensive management approach.

This is the prospective, observational cohort study (Nezha) to explore the associations of sleep disturbance with progression, efficacy of immune checkpoint inhibitors (ICIs) and prognosis of Lung Cancer. The participants including the patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who received either first-line therapy (ICIs or targeted agents) or neoadjuvant therapy with ICIs; patients diagnosed with advanced small-cell lung cancer (SCLC) receiving the first-line therapy ICIs; patients diagnosed with early non-small-cell lung cancer (NSCLC) receiving surgery.

The goal of this clinical trial is to learn if human interleukin-2 (IL-2) works to treat moderate to severe chronic spontaneous urticaria in adults who remain symptomatic despite oral antihistamine treatment (refractory CSU). It will also learn about the safety of IL-2. The main questions it aims to answer are: Does IL-2 alleviate the symptoms of urticaria in patients? What medical problems do participants have when given IL-2? Researchers will compare IL-2 to a placebo (a look-alike and smell-like substance that contains no IL-2) to see if IL-2 works to treat refractory, moderate to severe CSU. Participants will: Receive IL-2 or a placebo intramuscular injections for 3 rounds at Week 0, 4 and 8, in which each round includes one injection daily for seven consecutive days. Visit the clinic for checkups and tests at Week 2, 4, 8, 12 and 24. Keep a diary of their symptoms and the number of tablets of oral antihistamines.

This is the prospective, observational cohort study (STRESS-LUNG) to explore the associations of psychological stress with progression, efficacy of immune checkpoint inhibitors (ICIs) and prognosis of Lung Cancer. The participants including the patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who received the first-line therapy or neoadjuvant therapy of ICIs; patients diagnosed with advanced small-cell lung cancer (SCLC) receiving the first-line therapy ICIs; patients diagnosed with early small-cell lung cancer (SCLC) receiving surgery.

The goal of this observational study is to learn about the molecular mechanisms underlying cardiovascular complications in individuals with type 2 diabetes (T2DM) and how they differ from healthy individuals. The study will also identify biomarkers and potential therapeutic targets for better managing diabetes-related heart disease. The main questions it aims to answer are: 1. What molecular changes are associated with cardiovascular complications in T2DM patients compared to healthy individuals? 2. How do genetic, gene expression, and protein profiles differ between T2DM patients with and without cardiovascular complications? Researchers will compare the molecular profiles of three groups: healthy controls, individuals with T2DM but no cardiovascular complications, and those with T2DM and cardiovascular complications. Participants will: 1. Provide blood samples for genomics, transcriptomics, and proteomics analysis 2. Undergo standard clinical tests such as blood pressure, echocardiogram, and ankle-brachial index measurements 3. Be followed for 12 to 24 months to track the development of cardiovascular events Participate in follow-up phone interviews to record major cardiovascular events like heart attacks or strokes

Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients. However, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term. This study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.