Effect of Protein Supplementation and Fluid Restriction on Plasma Sodium Levels in Patients Undergoing Pituitary Surgery

NCT ID: NCT07273630

Last Updated: 2026-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-20
• Study Completion Date: 2028-10-01

Brief Summary

The investigators are conducting this study to investigate new preventive measures for patients with low sodium levels (hyponatremia), which can occur after surgery on the pituitary gland. This hyponatremia is often caused by the syndrome of inappropriate antidiuresis (SIAD). SIAD occurs when the pituitary gland secretes too much antidiuretic hormone. The antidiuretic hormone causes the kidneys to absorb more water. This dilutes the sodium in the blood and leads to hyponatremia. Low sodium levels are particularly common after pituitary surgery, as the procedure on the pituitary gland can lead to increased reactive secretion of antidiuretic hormone. At present, apart from educating patients about the symptoms of hyponatremia, there are no established standard measures for prevention after pituitary surgery. If hyponatremia is present, it is currently treated primarily by fluid restriction, which is not always pleasant or easy to adhere to. With this study, the investigators want to investigate whether protein supplementation or fluid restriction between day 4 and day 9 after surgery can serve as a preventive measure to stabilize sodium levels after pituitary surgery and improve the quality of life of patients.

Detailed Description

Disturbances in water balance, often due to disturbed arginine vasopressin (AVP) secretion from pituitary stalk and/or posterior lobe damage/manipulation, are common complications following pituitary surgery. This can result in either AVP deficiency, causing polyuria and polydipsia, or AVP excess, leading to water retention and dilutional hyponatremia (syndrome of inappropriate antidiuresis, SIAD). SIAD affects up to 30% of patients, typically developing between days 4 and 14 post-surgery, with a peak around day 7. While usually mild, severe hyponatremia is a leading cause of hospital readmission. Management includes fluid restriction, oral urea, or, in severe cases, hypertonic saline and AVP receptor antagonists.

Non-medicinal preventive strategies, such as prophylactic fluid restriction, have demonstrated efficacy in reducing SIAD incidence and hospital readmissions, but the optimal protocol remains unestablished. Dietary protein supplementation has recently emerged as a potential novel intervention, leveraging osmotic diuresis from increased endogenous urea production derived from the physiological amino-acid metabolism to raise plasma sodium levels. However, no data in the postoperative setting are available

This study aims to compare protein supplementation and fluid restriction to standard care (no specific intervention) in preventing post-pituitary surgery hyponatremia. From days 4 to 9 post-surgery, participants will receive one of the three treatments: Treatment A: Patients will limit their total daily fluid intake to a maximum of 1000 ml Treatment B: Patients will consume an additional 80 grams of protein daily through two 150 ml protein drinks (40 grams of protein each, MOLTEIN PURE Drink, OMANDA) in various flavors. Treatment C: Patients will not receive specific instructions. They will follow standard post-operative care and serve as a control group.

Conditions

Hyponatremia; Pituitary Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Limited fluid intake

Patients will limit their total daily fluid intake

Group Type: EXPERIMENTAL

Fluid restriction

Intervention Type: DIETARY_SUPPLEMENT

Patients will limit their total daily fluid intake to a maximum of 1000 ml, including any liquids of their choice, such as water, milk, or juice.

Additional protein

Patients will consume additional protein daily

Group Type: EXPERIMENTAL

Dietary protein supplementation

Intervention Type: DIETARY_SUPPLEMENT

Patients will consume an additional 80 grams of protein daily through two 150 ml protein drinks (40 grams of protein each, MOLTEIN PURE Drink, OMANDA) in various flavors. They can distribute the drinks throughout the day and drink other fluids freely based on thirst.

No instructions

Patients will not receive specific instructions.

Group Type: ACTIVE_COMPARATOR

Standard post-operative care

Intervention Type: DIETARY_SUPPLEMENT

Patients will not receive specific instructions on protein supplementation or fluid restriction. They will follow standard post-operative care and drink or eat freely based on natural appetite and thirst.

Interventions

Fluid restriction

Patients will limit their total daily fluid intake to a maximum of 1000 ml, including any liquids of their choice, such as water, milk, or juice.

Intervention Type: DIETARY_SUPPLEMENT

Dietary protein supplementation

Patients will consume an additional 80 grams of protein daily through two 150 ml protein drinks (40 grams of protein each, MOLTEIN PURE Drink, OMANDA) in various flavors. They can distribute the drinks throughout the day and drink other fluids freely based on thirst.

Intervention Type: DIETARY_SUPPLEMENT

Standard post-operative care

Patients will not receive specific instructions on protein supplementation or fluid restriction. They will follow standard post-operative care and drink or eat freely based on natural appetite and thirst.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Adult patients (aged 18 or older) undergoing trans-sphenoidal or trans-cranial surgery for sellar / suprasellar pathology
• No pre-existing AVP-deficiency and SIAD or other causes of hyponatremia

Exclusion Criteria

• AVP deficiency diagnosed before surgery based on established criteria
• Other type of neurosurgery / intracranial pathology / pre-existing spontaneous CSF -rhinorrhea
• Traumatic brain injury or intracranial hemorrhage
• Systemic infection or other causes for systemic stress
• Lactose intolerance, milk protein allergy, soy allergy, nuts allergy or known hypersensitivity or allergy to one of the components of the protein supplementation
• Inborn metabolic disorders implying carbohydrate, lipid, or protein metabolism
• Severe hepatic impairment (ALAT/ASAT >3x upper limit) or advanced symptomatic liver disease defined as past or current hepatic encephalopathy, liver cirrhosis Child C, or decompensated (bleeding, jaundice, hepatorenal syndrome)
• Reduction of eGFR <45 mL/min/1.73m² (KDIGO G3b, G4 and G5) or end stage renal disease (dialysis)
• Recently initiated (within the last 5 days) SGLT2 inhibitors, vaptans, or oral urea therapy
• Pregnancy or breastfeeding
• Lack of capacity or other reason preventing from giving informed consent or following study procedures.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirjam Christ-Crain, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Endocrinology

Locations

University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Mirjam Christ-Crain, Prof. Dr. med.

Role: CONTACT

Mirjam.Christ-Crain@usb.ch

0041 61 328 70 80

Michelle Mueller

Role: CONTACT

0041 61 328 55 23

Facility Contacts

Michelle Muelle

Role: primary

michelle.mueller@usb.ch

+41 61 32 85523

Other Identifiers

2025-01549; kt25ChristCrain

Identifier Type: -

Identifier Source: org_study_id