AAV BBP-631 for Adrenocortical Hyperfunction
This study is evaluating whether a new gene therapy may help treat a rare disease.
See full descriptionAbout the trial for Adrenocortical Hyperfunction
Treatment Groups
This trial involves 3 different treatments. AAV BBP-631 is the primary treatment being studied. Participants will be divided into 3 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.
Eligibility
This trial is for patients born any sex aged 18 and older. There are 6 eligibility criteria to participate in this trial as listed below.
Approximate Timelines
Measurement Requirements
This trial is evaluating whether AAV BBP-631 will improve 2 primary outcomes and 3 secondary outcomes in patients with Adrenocortical Hyperfunction. Measurement will happen over the course of Baseline, Week 52.
Patient Q & A Section
Can adrenocortical hyperfunction be cured?
In the past, the term "adrenalectomy" has implied the surgical removal of the entire adrenal gland and the patient as a whole. However, as surgeons became more comfortable excising only adenomas, they realized that there was a higher probability of cure when removing only the adenoma instead of the complete gland. If the patient's adenomas can be accurately identified by an experienced endocrinologist of good surgical credentials, complete adrenalectomy may no longer be an absolute indication for treatment of adrenal cancer. Further studies will need to be done to compare the probability of cure if only adenomas are excised versus complete glandectomy in appropriately selected patients.
How many people get adrenocortical hyperfunction a year in the United States?
Recent findings, we found no evidence that adrenal insufficiency is more common among people who have had a diagnosis of autoimmune thyroiditis than among the general population. However, one study has reported increased prevalence of adrenal insufficiency among patients with Graves' disease, but another study found no differences in prevalence of adrenal insufficiency among these and non-autoimmune thyroid disease. Therefore, the relationship of adrenal insufficiency to autoimmune thyroiditis is controversial and needs further study before it can be accepted as a marker for the autoimmune process at large.
What causes adrenocortical hyperfunction?
The mechanism which results in high levels of cortisol in the blood may be the cause of many different diseases. In severe disease such as Addison's disease, the adrenal cortex will produce excess steroid hormones, which lead to the overactive steroidogenesis. In Addison's disease this process may proceed, although in many individuals the overactive part of the adrenal cortex dies off after a period of time. In adrenocortical carcinoma, though the adrenal cells are not overwhelmed by a hyperplasia but the production of the adrenocortical hormones is abnormally increased. The hypersecretion of adrenocortical hormones in both Addison's disease and in adrenocortical carcinoma appears to act as a tumour promoter.
What are the signs of adrenocortical hyperfunction?
HPA axis deficiency is frequently associated with clinical signs of distress and may thus mimic Cushing's syndrome and Addisonism. It also may play a key role in CFS.
What is adrenocortical hyperfunction?
Adrenocortical hyperfunction is common in the ICU population and can result from a common mechanism in that region, such as sepsis. As the majority of patients with ACH have normal adrenal function before their ICU stay, the presence of steroid-responsive illnesses must also be considered.
What are common treatments for adrenocortical hyperfunction?
Severe hypokalaemic adrenocortical insufficiency needs close medical monitoring, and can rarely be treated surgically. Glucocorticoids may be of temporary benefit but long-term glucocorticoid treatment should be avoided as this leads to glucocorticoid resistance. There is currently no cure for glomerulonephritis. Severe cases need aggressive antifungal therapy, with long-term therapy more commonly used, leading to resistance. Other treatment of glomerulonephritis include ACEIs, ARBs or statins. Kidney transplantation is indicated in more severe cases.
What are the common side effects of aav bbp-631?
For this trial, the most common side effects were headache and decreased appetite. The most common side effects in patients treated with avitapine were decreased appetite and insomnia. Side effects in the control trials were relatively mild and did not preclude aav bbp-631 from further investigation for treatment of depression.
Have there been any new discoveries for treating adrenocortical hyperfunction?
A few new discoveries have been proposed for the treatment of ACTH oversecretion, including the treatment of comorbidity, the role of metyrapone infusion, and a therapy to reduce the effects of cortisol's positive feedback (including administering glucocorticoid antagonists such as prednisolone and prednisone) upon adrenocortical hyperfunction.
Does aav bbp-631 improve quality of life for those with adrenocortical hyperfunction?
Among patients with ACTH-independent Cushing's syndrome, Cushing's syndrome patients with adrenocortical insufficiency and the patients with ACTH insufficiency are all more sensitive to the acute stress of ACTH therapy with aav bbp-631 than patients with normal cortisol secretion.
What is the average age someone gets adrenocortical hyperfunction?
Adrenal gland hyperfunction is a serious medical condition that can be life-threatening in childhood and early adulthood. The median age of adrenal hyperfunction onset is 8 years old and the median age of adrenal function remission is 17 years old. Adrenal hyperfunction affects girls and boys equally and should be considered when evaluating a child who complains of abnormal adrenal gland function. We can never know the actual incidence of adrenal hyperfunction because many patients never seek medical attention because they think it normal to have adrenal dysfunction.
Who should consider clinical trials for adrenocortical hyperfunction?
A substantial number of patients with adrenocortical hyperfunction are not thought to have an improvement in their steroid responsiveness and therefore do not meet the criteria for clinical trials. Patients with adrenocortical hyperfunction should be encouraged to participate in an ACRRA clinical trial for at least 4 months to minimize the risk of under-recognition and treatment. In a recent study, findings have important implications for adrenal imaging studies in the diagnostic evaluation of all patients with exogenous sources of corticosteroids.
What are the latest developments in aav bbp-631 for therapeutic use?
The data submitted in this letter indicate that, in our opinion, the development data of aav bbp-631 are comparable, if not better, than those of TU-104 in terms of [safety] and pharmacology. Both aav bbp-631.0120(a) and aav bbp-631(b) are in clinical development (approved only in the US and Europe).