Ignite Creation Date:
2024-05-05 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00149721
Status:
TERMINATED
Last Update Posted:
2010-03-02
First Post:
2005-09-07
Brief Title:
Anterior Pituitary Function in Patients With Hydrocephalus
Sponsor:
Johns Hopkins University
Organization:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Study Overview
Official Title:
Anterior Pituitary Function in Patients With Hydrocephalus
Status:
TERMINATED
Status Verified Date:
2010-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hydrocephalus secondary or idiopathic is a condition characterized by dilatation of the lateral and third ventricles and often associated with increased intracranial pressure ICP We hypothesize that either the ventricle dilatation or the increased ICP may cause disturbances in the hypothalamic-pituitary axis resulting in different degrees of hypopituitarism The goal of this study is to determine the prevalence of hypopituitarism in adult patients with hydrocephalus
Detailed Description:
The Johns Hopkins Adult Hydrocephalus Program evaluates approximately 250 new patients per year for hydrocephalus and associated disorders resulting in the new diagnosis of hydrocephalus in about 100 patients annually After treatment with either shunt surgery or third ventriculostomy virtually all patients are followed on a regular basis by physicians in the program Dr Michael Williams neurologist and Dr Daniele Rigamonti neurosurgeon both involved in this project
These patients represent an ideal cohort to study the effect of hydrocephalus on anterior pituitary function In addition as data on intracranial pressure is available for all of them evaluation of pituitary function would allow us to determine whether the level of intracranial pressure correlates with the likelihood of pituitary failure
We propose to study 20 subjects of both sexes with NPH aged 18-80 years over a period of 18 months They will be recruited by direct advertising among the patients cared for by the Adult Hydrocephalus Program Patients with hydrocephalus will be studied twice 6-12 months apart whether or not they undergo shunting
STUDY PROTOCOL
1 In addition to the comprehensive neurological history and physical examination further history will be obtained with particular attention to sexual function and libido in males and menstrual history in women of fertile age will be collected
2 After overnight fasting an indwelling catheter will be inserted in a peripheral vein Blood for baseline hormonal evaluation 8-9 AM including serum free T4 FT4 TSH cortisol GH IGF-1 prolactin LH FSH Estradiol in females and total testosterone in males Menstruating females will be studied during follicular phase Serum IGF-1 testosterone estradiol and gonadotropin levels will be interpreted in accordance with the patients age
3 All subjects will undergo GH stimulation test by combination of GHRH 1 mcgkg bolus and arginine 05 gmkg over 30 maximal dose 30 gm Blood will be dawn at time 30 60 90 and 120 after the GHRH bolus injection The GHRHarginine test is the most widely used test to determine GH reserve in adults independently from their age 14 Normal response is a peak serum GH 9 ngml Both GHRH and arginine are FDA-approved for this purpose and have no significant side effects GHRH may cause transient itching and flushing
4 An AM cortisol below 5 mcgdl will be considered diagnostic of adrenal insufficiency Conversely a value above 15 mcgdl will be interpreted as indicating normal adrenal function For serum cortisol values between 5 and 15 mcgdl subjects will be studied on a separate day by low-dose 1 mcg ACTH stimulation test Blood for serum cortisol measurement will be obtained at baseline and after 30 from ACTH injection The low-dose ACTH stimulation test is safe easy to perform has high sensitivity for partial secondary adrenal insufficiency and has been recently used in patient with TBI Normal response is a serum cortisol at 30 180 mcgdl
Subjects who have shunt surgery will undergo a second study of pituitary function not earlier than 6 months and no later than 1 year from the procedure We will identify the degree of clinical improvement by documenting change in gait with the Tinetti Gait Assessment Tool and change in dementia with the Mini-Mental-Status exam If there is sufficient sample size in the clinically improved and unimproved patients we will compare between-group results
Patients who have been on systemic glucocorticoids GC for longer than 3 weeks during the previous 12 months will be excluded as GC may cause suppression of hypothalamic-adrenal axis In subjects who are on phenytoin unbound T4 will be measured by equilibrium dialysis as phenytoin may interfere with direct unbound T4 measurement Subjects already on L-thyroxine replacement will be excluded
These patients represent an ideal cohort to study the effect of hydrocephalus on anterior pituitary function In addition as data on intracranial pressure is available for all of them evaluation of pituitary function would allow us to determine whether the level of intracranial pressure correlates with the likelihood of pituitary failure
We propose to study 20 subjects of both sexes with NPH aged 18-80 years over a period of 18 months They will be recruited by direct advertising among the patients cared for by the Adult Hydrocephalus Program Patients with hydrocephalus will be studied twice 6-12 months apart whether or not they undergo shunting
STUDY PROTOCOL
1 In addition to the comprehensive neurological history and physical examination further history will be obtained with particular attention to sexual function and libido in males and menstrual history in women of fertile age will be collected
2 After overnight fasting an indwelling catheter will be inserted in a peripheral vein Blood for baseline hormonal evaluation 8-9 AM including serum free T4 FT4 TSH cortisol GH IGF-1 prolactin LH FSH Estradiol in females and total testosterone in males Menstruating females will be studied during follicular phase Serum IGF-1 testosterone estradiol and gonadotropin levels will be interpreted in accordance with the patients age
3 All subjects will undergo GH stimulation test by combination of GHRH 1 mcgkg bolus and arginine 05 gmkg over 30 maximal dose 30 gm Blood will be dawn at time 30 60 90 and 120 after the GHRH bolus injection The GHRHarginine test is the most widely used test to determine GH reserve in adults independently from their age 14 Normal response is a peak serum GH 9 ngml Both GHRH and arginine are FDA-approved for this purpose and have no significant side effects GHRH may cause transient itching and flushing
4 An AM cortisol below 5 mcgdl will be considered diagnostic of adrenal insufficiency Conversely a value above 15 mcgdl will be interpreted as indicating normal adrenal function For serum cortisol values between 5 and 15 mcgdl subjects will be studied on a separate day by low-dose 1 mcg ACTH stimulation test Blood for serum cortisol measurement will be obtained at baseline and after 30 from ACTH injection The low-dose ACTH stimulation test is safe easy to perform has high sensitivity for partial secondary adrenal insufficiency and has been recently used in patient with TBI Normal response is a serum cortisol at 30 180 mcgdl
Subjects who have shunt surgery will undergo a second study of pituitary function not earlier than 6 months and no later than 1 year from the procedure We will identify the degree of clinical improvement by documenting change in gait with the Tinetti Gait Assessment Tool and change in dementia with the Mini-Mental-Status exam If there is sufficient sample size in the clinically improved and unimproved patients we will compare between-group results
Patients who have been on systemic glucocorticoids GC for longer than 3 weeks during the previous 12 months will be excluded as GC may cause suppression of hypothalamic-adrenal axis In subjects who are on phenytoin unbound T4 will be measured by equilibrium dialysis as phenytoin may interfere with direct unbound T4 measurement Subjects already on L-thyroxine replacement will be excluded
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None