Our current pituitary-related clinical trials and other research efforts are summarized below:
1. Treatment of Cushing’s Disease With Seliciclib : CURRENTLY ENROLLING
Seliciclib (also known as roscovitine) is an investigational medication that is not FDA approved. It is administered orally for 4 days every week for 4 weeks at one of 3 doses/schedules being studied. You will be required to participate in 7 clinic visits, including a screening visit, a baseline visit, weekly visits while on drug treatment, and a final visit at study completion. Routine history and physical with blood, urine tests, ECG, visual field test, and pituitary MRI will be obtained during the visit.
• Pituitary ACTH-producing tumor causing Cushing disease, including newly diagnosed Cushing’s disease or recurrent or persistent Cushing’s disease despite standard treatment
• Persistently elevated urinary cortisol levels
This study (NCT03774446) is being conducted in collaboration with Cedars Sinai Medical Center. Please contact the Pituitary Disorders Center at Pacific Neuroscience Institute for more information | 310-582-7450 | Download PDF flyer
2. Corcept for Cushing’s Disease: CURRENTLY ENROLLING
Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant (NCT03697109). Download PDF flyer
3. TRANSSPHER Study in Pituitary Patients Comparing Microscopic and Endoscopic Surgical Techniques: TRANSSPHER study is a prospective, observational study comparing extent of tumor resection between microscopic transsphenoidal surgery and fully endoscopic transsphenoidal surgery for nonfunctioning macro-adenomas. The most widely accepted surgical technique is microscopic transsphenoidal surgery, in which an operating microscope is used by the surgeon to provide surgical visualization and a nasal speculum is used to maintain the operative corridor. Recently, fully endoscopic transsphenoidal surgery, in which surgical visualization is achieved using an endoscope, has been adopted by many pituitary surgeons because the technique offers superior panoramic and angled visualization of the surgical target and may permit greater tumor resection. There is a vigorous debate in the neurosurgical community about the relative merits of the microscopic and endoscopic techniques. Proponents of the endoscopic technique argue that the superior visualization permits more aggressive tumor resection and better preservation of the normal pituitary gland. Proponents of the microscopic technique argue that it permits shorter operative times, results in similar surgical outcomes, and has a lower complication rate. This is a multi-center study conducted with the Barrow Neurological Institute.
4. Pituitary Tumor Biomarker Studies: This is an ongoing study aimed at gaining a better understanding of pituitary tumor genetics and growth patterns to plan more effective treatments beyond surgery. All patients undergoing removal of a pituitary tumor or related skull base tumor (chordoma, craniopharyngioma, meningioma) are eligible to participate. For participants, a portion of their tumor specimen removed at surgery is placed in a tumor repository. Tumor cells are then studied for specific genetic markers that may indicate their aggressiveness or potential responsiveness to various therapies such as a chemotherapy, immunotherapy or radiosurgery. This is study is being performed in collaboration with Dr. Dave Hoon, Director of Molecular Oncology at JWCI.
- Pituitary Adenoma Genetic Analysis: Though generally benign (non-cancerous), pituitary adenomas can be invasive and some aggressive (“atypical”) subtypes can be difficult to treat effectively. This study analyzes the genetic composition of these tumors in order to identify potential genetic targets that can explain tumor pathogenesis and potentially serve as therapeutic targets. This study is being performed with Dr. Dave Hoon at the John Wayne Cancer Institute. It is funded by a grant from Carol Zumbro.
- Endocrine Active Pituitary Adenoma Genetic Study: Among pituitary adenomas, those that are hormone secreting can be more difficult to treat successfully. Even a small amount of residual tumor can still result in significant medical maladies and can affect quality of life. This study analyzes the genetic profiles of hormone secreting pituitary adenomas, particularly in the setting of acromegaly. It also is evaluating the effect of somatostatin analogues on these tumors. This study is funded by Novartis Pharmaceuticals, Inc.
5. Ongoing Retrospective Pituitary-Related Studies: We are constantly looking for ways to improve the surgical and medical therapy we provide to our patients with pituitary tumors. Hence, we are actively involved in reviewing the numerous surgical operations and medications we offer our patients. We study patient outcomes including tumor remission or cure rates, improvement of pre-operative symptoms, post-operative management, and rates of treatment complications. A list of our most recent publications can be found here.
6. Skull base and Endoscopic Microdissection Laboratory: An integral component of cutting edge neurosurgery is an intimate understanding of the microsurgical anatomy of our patients. To further our knowledge in this field, we have established the Skull-base and Endoscopic Microdissection Laboratory. This facility offers our fellows and researchers a high-quality facility equipped with state-of-the-art neuronavigation, endoscopy, microscopy, instrumentation and HD video recording technology to perform high quality microsurgical dissections. Such an effort will improve our understanding of the relevant anatomy and its variations across patients. In addition, it will serve as an important training venue for our rotating surgical fellows. This project has been supported by in-kind donations from: Stryker, Karl Storz Endoskope, Surgical West, Inc., and Mizuho.
7. Hypopituitarism (Pituitary Gland Dysfunction) in Retired Professional Football Players: Pituitary gland and related hormonal dysfunction is a known consequence of severe traumatic brain injury (TBI). The impact of repeated mild TBI (concussion) that may occur in contact sports is less clear. In this study published in Journal of Neurotrauma (2014)“Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study.” (see Pubmed link), we assessed the relationship between concussion, subsequent hormonal function, neurobehavioral deficits and quality of life (QOL) in retired NFL players. From a database of 2800 retired NFL players, 74 retirees with poor quality of life, age 30 – 65 years were studied with hormonal, neurobehavioral and QOL testing from early 2009 to June 2012.
- Abstract: Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30-65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI. (This study was sponsored by National Operating Committee on Standards for Athletic Equipment (NOCSAE) and by Pfizer, Inc. Co- Principal Investigators: Daniel Kelly (JWCI) and Kevin Guskiewicz (University of North Carolina).