Clinical Research Directory

Mitochondrial Redox Modulation in Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Trial Comparing Imeglimin vs. Metformin Monotherapy

he goal of this clinical trial is to compare the mitochondrial redox effects of imeglimin versus metformin monotherapy in adults with newly diagnosed Type 2 diabetes mellitus who are treatment-naive. The main questions it aims to answer are: Does imeglimin improve the fasting plasma pyruvate/lactate ratio (a validated surrogate of mitochondrial NAD⁺/NADH redox balance) to a greater extent than metformin after 12 weeks of treatment? Does imeglimin produce more favorable changes in secondary mitochondrial and glycemic biomarkers - including fasting plasma lactate, fasting plasma pyruvate, HbA1c, HOMA-IR, and lipid profile - compared to metformin? Researchers will compare imeglimin 1000 mg twice daily to metformin up to 1000 mg twice daily to see if imeglimin produces superior improvement in mitochondrial oxidative capacity and cytoplasmic redox balance, reflected by a greater increase in the fasting plasma pyruvate/lactate ratio, without compromising glycemic efficacy or safety. Participants will: Take either imeglimin 1000 mg twice daily or metformin (titrated up to 1000 mg twice daily) orally for 12 weeks, as assigned by randomization Attend clinic visits at baseline (Week 0) and at Week 12 for fasting blood sample collection, including strict bedside deproteinization of pyruvate samples using ice-cold perchloric acid to ensure analytical accuracy Undergo measurement of fasting plasma pyruvate/lactate ratio, HbA1c, HOMA-IR, fasting glucose, fasting insulin, fasting plasma lactate, fasting plasma pyruvate, and full lipid profile at both visits Be monitored for adverse events and safety parameters, including renal function (eGFR), throughout the study period

Adipose Stem Cell Mitochondria Supplementation to Oocytes (ASCENT)

The purpose of this study is to investigate the potential of autologous adipose stem cell (ASC) mitochondrial transfer (ASCENT) to oocytes along with intracytoplasmic sperm injection (ICSI)as a means of enhancing embryo development and improving the success rate of in patients with a history of multiple IVF failures. Embryo quality plays a crucial role in determining the success of assisted reproductive technologies and directly contributes to repeated pregnancy failures. Several factors, including age, physiological conditions, genetics, and environmental influences, can significantly impact embryo quality. Oocytes, the largest cells in the human body, are heavily reliant on mitochondria. Mitochondria's role in providing energy for oocytes is crucial, and insufficient energy production has been linked to poor oocyte and embryo quality. Some human studies have shown that increasing oocyte mitochondrial mass can improve embryo quality in patients who have experienced repeated IVF failures.

Cancer-associated Muscle Mass - Molecular Factors and Exercise Mechanisms

Muscle mass loss is a common adverse effect of cancer. Muscle mass loss occurs with or without reduction in body weight. Cancer cachexia (CC) is the involuntary loss of body weight of \>5% within 6 months and it occurs in 50-80% of patients with metastatic cancer. It is estimated that CC is a direct cause of up to 30% of all cancer-related deaths. No treatment currently is available to prevent CC, likely because the chemical reactions that causes of this devastating phenomenon in unknown. No treatment currently is available to prevent muscle mass loss in patients with cancer but is urgently needed as the reduced muscle mass and function is associated with impaired physical function, reduced tolerance to anticancer therapy, poor quality of life (QoL), and reduced survival. There is evidence of an interdependence between informal caregiver (e.g. spouse) and patient QoL. Thus, identifying caregiver distress and needs can potentially benefit QoL for patients with cancer cachexia. Despite the enormous impact on disease outcomes, it is not known why the loss of muscle mass and function occurs and very few studies have investigated the underlying molecular causes in humans. In particular, there is a severe lack of studies that have obtained human skeletal muscle and adipose tissue sample material. Such reference sample materials will be invaluable to obtaining in-depth molecular information about the underlying molecular causes of the involuntary but common muscle mass and fat mass loss in cancer. At a whole body level, cancer cachexia is associated with reduced sensitivity to the hormone insulin, high levels of lipids in the blood, and inflammation. Within the skeletal muscle, the muscle mass loss is associated with elevated protein breakdown and reduced protein build-up while emerging, yet, limited data also suggest malfunction of the power plants of the cells called mitochondrions. The role of malnutrition and how it contributes to weight loss is understood only to the extent of the observed loss of appetite and the reduced food intake because of pain, nausea, candidiasis of the mouth, and breathlessness. Evidence is increasing that the environment of the intestinal system could be implicated in cancer cachexia, yet, the possible effect of cancer and the cancer treatment on the intestinal environment is not understood. Thus, large and as yet poorly understood details of this syndrome precede a later weight loss. Exercise training could help restore muscle function and how the chemical reactions works in cancer. In healthy people, and patients with diabetes, cardiovascular disease, and obesity exercise potently improves health. Exercise has been thought to slow down the unwanted effects of cancer cachexia by changing the reactions mentioned above. Thus, there is a tremendous gap in our knowledge of how and if exercise can restore the cells power plants function, muscle mass, strength, and hormone sensitivity in human cachexic skeletal muscle. Tackling that problem and examining potential mechanisms, will enable us to harness the benefits of exercise for optimizing the treatment of patients with cancer. The data will provide novel clinical knowledge on cachexia in cancer and therefore addressing a fundamental societal problem. Three specific aims will be addressed in corresponding work packages (WPs): * investigate the involvement of hormone sensitivity of insulin and measure the chemical reactions between the cells in patients with lung cancer (NSCLC) and describe the physical performance and measure amount of e.g. muscles and adipose tissue across the 1st type of cancer treatment and understand how that is related to the disease and how patients and informal caregiver feel (WP1). * find changes in the chemical reactions in skeletal muscle, adipose tissue (AT), and blood samples in these patients, to understand how to predict how the disease will develop (WP2). * measure changes of skeletal muscle tissue in response to exercise and see if it might reverse the hormone insensitivity and improve muscle signaling and function (WP3). The investigators believe that: * the majority of patients with advanced lung cancer, at the time of diagnosis already are in a cachectic state, where they lose appetite, and have hormonal changes, and an overall altered chemical actions between the cells affecting both muscle mass and AT. The investigators propose that all this can predict how the disease will progress, and how patient- and informal caregiver fell and how they rate their quality of life. * lung cancer and the treatment thereof is linked with changes in the blood, the muscle tissues, and the adipose tissues, especially in patients experiencing cachexia, that could be targeted to develop new treatment. * exercise can restore the muscles and improve insulin sensitivity and improve the function of the cells power plants in patients with lung cancer-associated muscle problems.