Preoperative Lanreotide Treatment in Acromegalic Patients With Macroadenomas

Study Overview
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Brief Summary
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Previous studies addressing preoperative somatostatin analogs (SSA) treatment and subsequent surgical cure rates are conflicting, reporting a benefit, or no difference between groups. And most reported studies were rather small and were made in retrospect, we conducted a prospective, randomized study to investigate whether 4-month preoperative lanreotide treatment would improve the surgical cure rate of newly diagnosed acromegalic patients with macroadenomas. The investigators also aimed to investigate whether there were differences in the incidence of surgical complications, and duration of neurosurgical hospital stay.

Detailed Description
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Acromegaly is a rare disease, caused by a growth hormone (GH)-secreting adenoma and in even more seldom instances (about 1%) due to excessive growth hormone-releasing hormone (GHRH) secretion, usually by a carcinoid tumor of the lung or gastrointestinal tract. The incidence of acromegaly is about 3-4 per 1 million per year and the prevalence is 60-70 per 1 million, without geographical or sex differences. Clinical features of acromegaly include acral enlargement, prognathism, jaw malocclusion, arthropathy, carpal tunnel syndrome, hyperhydrosis, sleep apnea, and visceromegaly. Transsphenoidal neurosurgery, allowing selective removal of the pituitary adenoma, is the current first treatment for acromegaly in the majority of patients. Its effects on GH and insulin-like growth factor I (IGF-I) secretion are rapid and operations have a low morbidity and very low mortality. However, surgery for macroadenomas causing acromegaly has a much lower surgical success rate than that for microadenomas. In experienced hands, microadenomas can be expected to be cured in around 90%, whereas with macroadenomas the figure is around 50%. This is particularly the case with tumours that extend into the cavernous sinus where surgical success is < 50%. Medical treatment of acromegaly with somatostatin analogs (SSAs) can lead to normalized GH and IGF-I levels and relief of symptoms. SSA treatment may cause shrinkage of GH-secreting pituitary adenomas. Theoretically, this could improve the likelihood of a radical resection, particularly in macroadenomas. Furthermore, it has been suggested that SSA treatment softens the tumor parenchyma and thereby facilitates tumor removal. Finally, it has been reported that SSA pretreatment leads to a shortening of postoperative hospital stay. Previous studies addressing preoperative SSA treatment and subsequent surgical cure rates are conflicting, reporting a benefit, or no difference between groups. And most reported studies were rather small and were made in retrospect, we conducted a prospective, randomized study to investigate whether 4-month preoperative lanreotide treatment would improve the surgical cure rate of newly diagnosed acromegalic patients with macroadenomas. We also aimed to investigate whether there were differences in the incidence of surgical complications, and duration of neurosurgical hospital stay.

Official Title
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A Prospective, Randomized Trial of Preoperative Lanreotide Treatment in Acromegalic Patients With Macroadenomas

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Preoperative lanreotide treatment
* Procedure: Transsphenoidal surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with newly diagnosed acromegaly due to GH-secreting macro-adenomas. newly diagnosed, previously untreated patients with GH nadir more than 2.5 μg/L during a standard 75-g, 2-h oral glucose tolerance test (OGTT) pituitary macroadenomas (maximum diameter >1 cm) verified by a pituitary magnetic resonance imaging (MRI) scan age between 18 and 80 yr. Exclusion Criteria: immediate surgery indicated by clinical criteria pregnancy contraindications to MRI scan patients judged not suitable to participate in the study for other reasons such as personality disorders and alcohol abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 2<br>After a baseline evaluation, patients underwent transsphenoidal surgery (direct surgery group). | Procedure: Transsphenoidal surgery<br> <br> |
| Experimental: Group 1<br>Patients received lanreotide for 16 weeks before the surgical resection [starting with 30 mg/2 weeks i.m. and increasing to 30 mg/week i.m. at week 8, if mean GH > 5 mU/L on GH day curve (GHDC)] (GHDC: 9×30-min samples collected in the morning after an overnight fast and rest, through an indwelling catheter inserted in an arm vein and while the patient was resting). | Drug: Preoperative lanreotide treatment<br>* Patients received lanreotide for 16 weeks before the surgical resection [starting with 30 mg/2 weeks i.m. and increasing to 30 mg/week i.m. at week 8, if mean GH > 5 mU/L on GH day curve (GHDC)] (GHDC: 9×30-min samples collected in the morning after an overnight fast and rest, through an indwelling catheter inserted in an arm vein and while the patient was resting).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure rate at evaluation 4 months postoperatively |  | every 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hospital stay duration |  | every 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acromegaly, Macroadenomas, Lanreotide, Transsphenoidal neurosurgery, Preoperative