Effect of Protein Supplementation and Fluid Restriction on Plasma Sodium Levels in Patients Undergoing Pituitary Surgery (TREASURE-PIT)

Effect of Protein Supplementation and Fluid Restriction on Plasma Sodium Levels in Patients Undergoing Pituitary Surgery - a Randomized Open-label Active-controlled Trial -

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.

Study Overview

• Status: Recruiting
• Conditions: Hyponatremia; Pituitary Surgery
• Intervention / Treatment: Dietary supplement: Fluid restriction; Dietary supplement: Dietary protein supplementation; Dietary supplement: Standard post-operative care

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.

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mirjam Christ-Crain, Prof. Dr. med.; Phone Number: 0041 61 328 70 80; Email: Mirjam.Christ-Crain@usb.ch
• Study Contact Backup: Name: Michelle Mueller; Phone Number: 0041 61 328 55 23

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Michelle Muelle; Phone Number: +41 61 32 85523; Email: michelle.mueller@usb.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Post-Inclusion Exclusion criteria (day 3 post-surgery, i.e.,time of randomization): - AVP deficiency diagnosed on post-operative day 3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Limited fluid intake; Patients will limit their total daily fluid intake	Dietary supplement: 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.
Experimental: Additional protein; Patients will consume additional protein daily	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.
Active Comparator: No instructions; Patients will not receive specific instructions.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds ratio of treatment failure (intervention compared to standard of care)	The primary objective is to evaluate the effectiveness of fluid restriction (Treatment A), and dietary protein supplementation (Treatment B) compared to the current standard care with no specific intervention and no fluid management guidance (Treatment C) in preventing treatment failure, defined at day 9 as a decrease in plasma sodium by at least 4 mmol/lL from baseline, and hyponatremia (plasma sodium <135mmol/L) or a decrease of at least 1 point in the MoCa score compared to baseline.	3 days post-surgery (time of randomization), and day 9 post-surgery.

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof. Dr. med., University Hospital Basel, Endocrinology

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 9, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: hyponatremia; protein supplementation; fluid restriction; postoperative hyponatremia; SIAD-related complications; Pituitary Surgery; Plasma Sodium Levels
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Nutritional and Metabolic Diseases; Hyponatremia
• Other Study ID Numbers: 2025-01549; kt25ChristCrain

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No