Prospective Study of Clinically Nonfunctioning Pituitary Adenomas (PAPS)
|First Received Date ICMJE||March 9, 2012|
|Last Updated Date||March 4, 2013|
|Start Date ICMJE||March 2009|
|Estimated Primary Completion Date||December 2016 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01556230 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Neurocognitive function change [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Change in neurcognitive function test score over the time frame of the study.
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Prospective Study of Clinically Nonfunctioning Pituitary Adenomas|
|Official Title ICMJE||Prospective Study of Clinically Nonfunctioning Pituitary Adenomas|
The purpose of this study is to carefully characterize the outcome of treatment for nonfunctioning pituitary adenomas. Pituitary adenomas are benign tumors of the pituitary gland. The study will follow 3 groups of patients with apparent pituitary adenomas (based on the MRI appearance and clinical presentation). One group of patients who will have surgery, a second who will not have surgery, and a third who have radiotherapy after surgery. The study will determine predictors of tumor growth and regrowth after surgery and if certain tumor markers can predict if the tumor will continue to grow. The study will determine whether the development of pituitary dysfunction, vision abnormalities or significant tumor growth differ between the no surgery, surgery, or radiation therapy groups. Patients in the study will also complete questionnaires on quality of life and memory function testing before and after the follow up or surgery or radiation treatment in order to determine if quality of life or memory are affected by these treatments.
This study conducts a comprehensive prospective study of clinically nonfunctioning pituitary adenomas. The study aims to test the hypothesis that conservative, nonsurgical management of clinically nonfunctioning pituitary lesions that do not meet criteria for surgery as initial therapy is safe with respect to changes in pituitary function, tumor size and visual and neurological function. The study also aims to determine the outcome of transsphenoidal surgery and also in some cases the addition of pituitary radiotherapy for symptomatic, clinically nonfunctioning pituitary tumors and test the hypothesis that radiotherapy will reduce the recurrence rate of pituitary tumors. In addition, the study will consider whether clinical features or immunohistochemical markers of tumor proliferation predict tumor regrowth. In particular the study will test the hypothesis that the silent corticotroph tumor subtype, characterized by elevated plasma levels of ACTH or its precursor, POMC, is associated with an increased tumor recurrence rate. The study also aims to determine for the first time, prospectively, the impact of conservative follow up, surgery and RT on quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions.
This project is the first comprehensive prospective study of clinically nonfunctioning pituitary adenomas (CNFAs). The purpose of the project is to answer a number of important questions about the evaluation and management of these lesions. No rigorously developed guidelines exist for the evaluation, therapy or longterm monitoring of CNFAs. Rather, current management strategies are loosely defined and based almost exclusively on data from retrospectively reported series. As a result, a number of significant gaps exist in our current knowledge about CNFA management. With regard to asymptomatic pituitary lesions, the appropriate initial evaluation and followup strategies, as well as the safety of conservative, nonsurgical management are unknown. For symptomatic tumors, surgery is the initial treatment of choice, but many tumors recur and there exists no means of reliably predicting those at risk for recurrence. Further study of predictors of aggressive, recurrent tumors is needed. One possible predictor requiring study is the "silent" corticotroph tumor type. The safety of conservative followup for patients with small tumor remnants after surgery is not known. The need for radiation for all such patients remains unclear since the risks vs. benefits of postoperative RT for residual/recurrent tumors have not been prospectively studied. The longterm management of CNFA should also consider the impact of therapy on quality of life and neurocognitive function, but these have never been evaluated longitudinally. Our large prospective study is needed to answer these important questions about CNFA management.
Study Design PROTOCOL I: Prospective Study of the outcome of conservative nonsurgical management of patients with asymptomatic, clinically nonfunctioning pituitary lesions. This protocol will evaluate prospectively the outcome of nonsurgical management of clinically nonfunctioning pituitary lesions that do not appear to need surgery as their initial therapy. The overall design consists of an initial baseline evaluation and then serial prospective follow up studies over time for up to 5 years of follow up. The study will evaluate laboratory testing, clinical examinations, quality of life and neurocognitive function in these patients. We will also collect data on visual fields and MRI studies of the pituitary tumor that are done prospectively as part of clinical care to evaluate these patients. Data to be collected will include the prevalence of pituitary dysfunction at presentation, the safety of conservative nonsurgical management of patients with asymptomatic, clinically nonfunctioning pituitary lesions with respect to the development of symptomatic tumor enlargement and pituitary dysfunction, the prevalence of the silent corticotroph tumor type that is characterized by elevated plasma levels of ACTH or its precursor, POMC, and if it is associated with an increased tumor recurrence rate and prospectively assess quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions treated without surgery.
PROTOCOL II : Prospective study of the outcome of patients with symptomatic, clinically nonfunctioning pituitary tumors who are treated with transsphenoidal surgery and in some cases also radiotherapy. This protocol will evaluate prospectively the outcome of surgical management of asymptomatic clinically nonfunctioning pituitary lesions. The overall design consists of an initial baseline evaluation and then serial prospective follow up studies over time with up to 5 years of follow up. The study will evaluate laboratory testing, clinical examinations, quality of life and neurocognitive function in these patients. We will also collect data on visual fields and MRI studies of the pituitary tumor that are done prospectively as part of clinical care to evaluate these patients. Data to be collected will be analyzed to determine the safety of observation alone following surgery for patients who do not have a clinically significant tumor remnant, if the silent corticotroph tumor type is characterized by elevated plasma levels of ACTH or its precursor, POMC, and if it is associated with an increased tumor recurrence rate. A group of patients who are planning RT will also be studied by these same procedures before and after RT in order to determine if the outcomes of patients who receive RT for treatment of tumor regrowth to that of those who do not receive RT with respect to further tumor growth, endocrine or neurological dysfunction. We will also prospectively assess quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions treated with surgery alone or those who also receive radiotherapy.
Group I: A group of 100 adult patients with pituitary lesions that do not require surgical intervention will be studied as part of Protocol I. Eligible patients will have a pituitary lesion demonstrated on MRI to be consistent with an adenoma (not a cystic lesion such as a Rathke's cleft cyst). Patients meeting any of the following indications for surgery will be excluded: presence of visual or neurological deficits due to the tumor, tumor impingement on the optic chiasm and physical or laboratory abnormalities consistent with a biologically active hormone secreting tumor. Some patients may have elevations of pituitary hormones such as ACTH, but no elevation of end organ hormone such as cortisol. Patients with a pituitary tumor that makes a functioning hormone and has a resultant biochemical and/or clinical syndrome associated with it would be treated as appropriate with surgery or medication and would not be followed conservatively without surgery.
Group II: A second group of 250 adult patients with pituitary lesions that require surgical intervention and who are planning on surgery will be studied as part of Protocol II. Although we have established general guidelines for who should be recommended for surgery, the formal decision whether or not to undergo surgery is a medical one made by the patient and the Neurosurgeon.
Group III: Patients who are undergoing Radiotherapy and previously underwent surgery for their pituitary tumor are also eligible to participate.
Patients in both study groups will be recruited directly from the office of the participating Neurosurgeon, Dr. Jeffrey Bruce and by referral to our Neuroendocrine Unit from the other participating Neurosurgeon, Dr. Kalmon Post.
Patients may also be recruited from out Neuroendocrine clinical practice or referred by outside physicians for participation in the study. Each patient will first be approached about participation in the study by their physician. It they are interested then the study team will discuss the study further with them.
Baseline Visit: History and physical examination, laboratory testing: prolactin, ACTH, cortisol, free thyroxine, TSH, LH, FSH, testosterone (men), GH, IGFI, POMC, asubunit, 24hour for urine free cortisol.
Follow up visits: 6 and 12 months and yearly after the baseline visit. Testing at each visit includes an update of the history, laboratory testing as done at the baseline visit, physical examinations and completion of quality of life and neurocognitive testing, visual field testing and pituitary MRI scans. Those patients who develop a clinically significant enlargement of the tumor that meets a surgical indication will be given the option of entering Protocol II. Tumor enlargement will be considered clinically significant if the tumor grows to impinge on the optic chiasm or causes any visual disturbance or other neurological abnormality.
Quality of life testing: Patients will be administered general health questionnaires SF36, NHP (Nottingham health profile) and disease specific questionnaires QLSH (quality of life satisfaction hypopituitarism) and QoL AGHD (Quality of life assessment of GH deficiency in adults). Neurocognitive testing: Patients will be administered a series of standard and widely used tests of neurocognitive function, primarily measures of memory and neurocognitive function, by trained personnel.
Protocol II Baseline Visit: History and physical examination, laboratory testing (as in Protocol I), visual fields, quality of life, neurocognitive testing (as in Protocol I) and MRI scan. Follow up visits after surgery: 6 and 12 months and yearly after the baseline visit include the testing as done at the baseline visit. Surgical procedures will take place as per routine clinical practice of the surgeon. Records from the surgical procedure including extent and invasion of the tumor and occurrence of endocrine abnormalities postoperatively such as diabetes insipidus or new hypopituitarism will be recorded. If patients are referred for radiotherapy if they have residual tumor or regrowth of their tumor then they will be followed also prospectively with a baseline visit and follow up visits after radiotherapy.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
Any persons diagnosed with a non-functioning pituitary adenoma that is willing to travel to our study center at Columbia University in New York, NY for all study visits.
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||350|
|Completion Date||Not Provided|
|Estimated Primary Completion Date||December 2016 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01556230|
|Other Study ID Numbers ICMJE||AAAE1260, R01NS070600|
|Has Data Monitoring Committee||No|
|Responsible Party||Pamela U. Freda, Columbia University|
|Study Sponsor ICMJE||Columbia University|
|Collaborators ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Information Provided By||Columbia University|
|Verification Date||March 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP