Clinical trials on Cushing’s syndrome

Cushing’s Syndrome

Cushing’s syndrome is a hormonal disorder caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol. This can occur either because of medications that increase cortisol levels or because the body itself produces too much cortisol. Cortisol is produced by the adrenal glands and is essential for a range of bodily functions, including the response to stress, metabolism of nutrients, and regulation of the immune system. When the balance of cortisol is disrupted, it leads to various symptoms and complications.

Complications

Cushing’s syndrome can lead to a variety of serious complications if not treated, impacting multiple systems in the body:
  • Cardiovascular complications: Increased risk of hypertension, heart disease, and stroke due to the persistent high levels of cortisol.
  • Metabolic issues: Development of type 2 diabetes and metabolic syndrome due to alterations in glucose metabolism and increased insulin resistance.
  • Bone health: Osteoporosis and increased risk of bone fractures due to decreased bone density and impaired calcium absorption.
  • Muscular and skin changes: Muscle weakness, loss of muscle mass, and thinning of the skin can occur, making the skin more susceptible to bruising.
  • Mental health issues: Increased prevalence of mood disorders such as depression and anxiety; cognitive impairments may also occur.
  • Immune system suppression: Higher susceptibility to infections due to impaired immune response.
  • Hormonal imbalances: Women may experience irregular menstrual cycles or amenorrhea, while men may have decreased fertility or sexual dysfunction.

Treatment Methods

The treatment of Cushing’s syndrome focuses on reducing the excessive levels of cortisol, either by treating the underlying cause or managing the effects of cortisol on the body. The most popular treatment methods include:
  • Surgery: Removal of the tumor that may be causing the increased production of ACTH (from the pituitary gland) or cortisol (from the adrenal glands) is often the first line of treatment.
  • Radiation therapy: Used primarily for pituitary tumors when surgery is not an option or has been unsuccessful.
  • Medication: Drugs such as ketoconazole, metyrapone, and mitotane can be used to reduce cortisol production. Medical therapies may also include medications to manage specific symptoms or complications like diabetes or hypertension.
  • Adrenalectomy: Surgical removal of one or both adrenal glands to directly curb cortisol production.

Prognosis

The long-term outlook for patients with Cushing’s syndrome varies depending on the cause and the effectiveness of the treatment. If the syndrome is caused by medication, prognosis is generally good if the medication is adjusted. However, if it is due to tumors or other internal causes, the prognosis depends on the success of the surgeries or treatments aimed at resolving the excess cortisol production.
  • CT-EU-00112069

    Exploring Abiraterone Acetate for Cushing’s syndrome in adrenocortical carcinoma patients

    This clinical trial is focused on exploring the effectiveness of a medication called Abiraterone Acetate (Zytiga) in treating patients with Adrenocortical Carcinoma (ACC) who are also experiencing Cushing’s Syndrome. ACC is a very rare type of cancer that can affect the adrenal glands, and about half of the adults with this condition have tumors that produce excess hormones, leading to Cushing’s Syndrome. This syndrome is characterized by an overproduction of cortisol, a hormone, which can cause various health issues and negatively impact the treatment outcomes for patients with ACC.

    The study is designed to see if Abiraterone Acetate can help control the levels of cortisol in the body. This medication works by blocking certain enzymes (17α hydroxylase/C17, 20-lyase) involved in the production of cortisol and androgen hormones. It’s already used in treating prostate cancer but hasn’t been tested for Cushing’s Syndrome before.

    There are two groups of patients in this study:

    1. Those with advanced or metastatic ACC who haven’t been able to control their Cushing’s Syndrome with the standard treatment, Mitotane, and possibly chemotherapy. These patients will receive Abiraterone Acetate alone, stopping Mitotane and chemotherapy, and will continue with this treatment until their condition progresses or their Cushing’s Syndrome is under control.

    2. Patients who are newly diagnosed with ACC and Cushing’s Syndrome and cannot undergo surgery. Initially, they will be treated with Abiraterone Acetate alone for 4 weeks, followed by a combination of Abiraterone Acetate and Mitotane, with or without chemotherapy, for 3 months.

    The main goal of the study is to see if Abiraterone Acetate can normalize the levels of a hormone called urinary free cortisol (UFC) within a month of starting treatment. UFC levels are a way to measure the amount of cortisol in the body. Safety and the management of any side effects are important aspects of this study. The medication will be taken orally, and if any adverse effects occur, dose adjustments may be made.

    • Abiraterone Acetate
  • A study of relacorilant in the treatment of hypercortisolism (Cushing’s syndrome) in patients with adrenal adenoma

    This clinical trial focuses on testing the effectiveness and safety of a drug called relacorilant in the treatment of patients with hypercortisolism (Cushing’s syndrome). Hypercortisolism is a condition in which there is too much cortisol in the body, which may occur due to an adenoma or hyperplasia of the adrenal glands that secrete cortisol. This condition can lead to diabetes or impaired glucose tolerance and/or uncontrolled high blood pressure.

    The study is in phase III, which means that the effectiveness and safety of the drug are compared with placebo. This is a double-blind, placebo-controlled study, which means neither participants nor researchers know who is receiving the actual drug and who is receiving the placebo to ensure unbiased results.

    Participants in this study will be randomly assigned to receive relacorilant or placebo for 22 weeks. The main goals of the study are to see how well relakorilant can improve blood sugar levels in patients with diabetes or impaired glucose tolerance, and how it affects blood pressure in people with high blood pressure. Additionally, the study will monitor the safety of relacorilant by recording any adverse events that occur.

    People who complete the study may have the opportunity to continue with a follow-up study, which may provide further information on the long-term effects and benefits of relacorilant.

    • Relacorilant
  • Long-term safety study of relacorilant for Cushing Syndrome patients

    The study is aimed at patients who have completed the Corcept-sponsored relacorilant trial. This is a continuation of that study. It is designed to assess the long-term safety of continuing treatment with relacorilant, a drug that targets the glucocorticoid receptor in the body that is involved in Cushing’s syndrome.

    The study is open-label, meaning that both the patient and the research team will know that they are receiving relacorilant. Treatment consists of taking relaxin capsules once a day. The dose of the drug can be adjusted depending on your response to treatment and any side effects you experience.

    The main aim of this study is to monitor the safety of relacorilant in the long term and, in particular, to check for any side effects that may occur during the 36 months of the study. This is an important step in understanding how relaxinib can be safely used in the long-term treatment of Cushing’s syndrome.

    This extended study offers the opportunity to continue treatment that may have been beneficial during the initial trial, with careful monitoring of health and safety.

    • Relacorilant
  • Exploring elagolix for mild cortisol excess in postmenopausal women

    The study involves postmenopausal women suffering from mild hypercortisolemia resulting from non-cancerous adrenal hyperplasia. The study examined whether a drug called elagolix, currently used to treat endometriosis, could help improve various health indicators and overall quality of life for these women.

    Mild hypercortisolism, or slightly elevated cortisol levels, can negatively impact the body, including changes in blood glucose and cholesterol levels, weight gain, and an increased risk of cardiovascular disease. The study aims to see if elagolix can lower cortisol production and therefore improve these conditions.

    During this 6-month study, participants will take elagolix 200 mg orally twice daily. Changes in cortisol levels will be monitored using a dexamethasone suppression test and 24-hour urine cortisol measurements at the beginning and end of the study. In addition, the size of the adrenal adenomas will be assessed using imaging techniques to see if any reduction has occurred.

    • Elagolix
  • Evaluating SPI-62 in treating ACTH-dependent Cushing’s Syndrome

    This is a study focused on a new treatment option for people suffering from ACTH-dependent Cushing’s syndrome, a condition often caused by a non-adrenal tumor. This condition leads to an overproduction of cortisol, which can have a significant impact on health. The study will test the efficacy and safety of a drug called SPI-62, which is designed to inhibit a specific enzyme involved in cortisol production.

    The study is structured as a randomized, placebo-controlled trial, meaning that participants will be randomly assigned to receive either SPI-62 or placebo treatment for a period of 24 weeks. Such a design helps ensure the reliability of the study’s results. Importantly, after this initial period, participants will have the option to continue the study and receive the active study drug, with follow-up visits every three months. The main goal of the study is to observe the change from baseline in urinary HSD-1 ratio, a marker that helps understand the activity of the enzyme targeted by SPI-62 in the liver. Participation in this study includes a screening period, a baseline period and a treatment period, with the possibility of a long-term extension for those who choose to continue.

    This trial represents a hopeful step forward for those affected by ACTH-dependent Cushing’s syndrome, offering a potential new treatment option that targets the condition at a molecular level.

    • SPI-62
  • Investigating the relationship between type 2 diabetes and Cushing’s Syndrome-treating patients with mifepristone

    This study is a Phase 4 clinical trial designed to explore the relationship between hypercortisolism (Cushing’s syndrome) and type 2 diabetes (T2D) that is difficult to control with standard treatments. This study is divided into two main parts. The first part, known as the Prevalence Phase, is an observational phase where researchers aim to find out how common hypercortisolism is among individuals with T2D who have an HbA1c level of 7.5% or higher, despite being on standard diabetes treatments. This phase does not involve any intervention.

    For those who qualify based on the results from the first part, the study moves into the second part, the Treatment Phase. In this phase, participants will be randomly assigned in a 2:1 ratio to either receive Korlym® (Mifepristone) 300 MG or a placebo (a pill without any active medication), taken once daily with food. The assignment to either group will also consider whether participants have an adenoma (a type of tumor) or not. This part of the study is designed to be double-blind, meaning neither the participants nor the researchers will know who is receiving the actual medication or the placebo. The goal here is to assess the safety and effectiveness of mifepristone in treating patients with hypercortisolism and T2D that is difficult to manage with standard care.

    The main thing researchers are looking to measure is the prevalence of hypercortisolism among participants in the first phase, and in the second phase, how well mifepristone can treat hypercortisolism in the context of difficult-to-control T2D. This study is being conducted at approximately 30 sites across the United States.

    • Mifepristone
  • SPI-62 as new drug for patients with ACTH-dependent Cushing’s syndrome

    This is a study focused on a new treatment option, SPI-62, for people struggling with ACTH-independent Cushing’s Syndrome. The main aim is to evaluate the efficacy and safety of SPI-62 in treating the condition.

    SPI-62 is a drug that works by inhibiting a specific enzyme in the body, potentially reducing excessive cortisol levels that contribute to the disease. During this study, participants will receive SPI-62 in oral tablet form. Dosing will vary, starting at a lower dose and potentially increasing depending on patient response and study requirements.

    The study has been designed as a Phase 2 trial, meaning that the primary focus is on understanding how well SPI-62 can treat the symptoms of hypercortisolism and what its safety profile is. Participants will be in the study for an extended period of time, with scheduled visits at baseline and then at 1, 3, 6, 9 and 12 months, followed by quarterly visits. These visits are crucial to monitor health status and treatment impact.

    One of the key aspects the researchers will be looking at is the change in HbA1c levels, a marker of blood sugar control, after both 6 and 12 weeks of treatment. This will help to understand whether SPI-62 can improve diabetes or the impaired glucose tolerance that often accompanies diabetes.

    • SPI-62- new potential medication for Cushing’s syndrome and Autonomous Cortisol Secretion
  • Exploring the safety and effectiveness of CRN04894 in treating Cushing’s syndrome

    This is a study to investigate a new treatment option for people suffering from Cushing’s syndrome, particularly those with ACTH-dependent conditions such as Cushing’s disease or ectopic ACTH syndrome (EAS). The study aims to evaluate the safety and effectiveness of a new drug called CRN04894, which is taken orally and works by acting on the ACTH receptor, potentially offering a new route to treating the disease.

    CRN04894 is a drug that has been developed to counteract the effect of ACTH on its receptor and is administered in the form of oral tablets. The study is an open-label, exploratory study, which means all participants will receive the actual drug and there will be no placebo group. Participants will take CRN04894 daily for a period of 10 days, followed by a 4-day monitoring phase to observe any changes and collect data on how the drug behaves in the body.

    The main goals of this study are to ensure the safety and tolerability of CRN04894, as well as to understand how the drug is processed by the body (pharmacokinetics) and its effect on certain disease-related biomarkers (pharmacodynamics). Key aspects that will be included any adverse events or side effects that occur, signs of adrenal insufficiency, and various laboratory test results. Additionally, circulating levels of CRN04894 will be closely monitored to better understand its effectiveness and optimal dosing.

    • CRN04894
  • Testing Osilodrostat treatment in Cushing’s disease in children aged 6 years to 17 years

    This study involves investigating a drug called osilodrostat in young individuals with Cushing’s Disease. The primary focus is to observe how the drug behaves and moves within the body, its impact on the disease, and its safety. The trial spans approximately 12 weeks, beginning with a period of abstaining from other medications that could influence cortisol levels, a hormone that becomes elevated in individuals with Cushing’s Disease. If positive effects persist after 12 weeks, the testing period may extend for an additional 9 months to evaluate the long-term influence of the drug on the disease and its safety. The study aims to assess the drug’s efficacy by comparing urine cortisol levels at the start and end of the trial.

    • Osilodrostat/LCI699