Creatine and Perioperative Brain Health (CREATE)

Creatine Intervention in Older Adults to Improve Perioperative Brain Health

The goal of this study is to understand the effects of oral creatine supplementation in the perioperative period. Creatine is commonly used to enhance athletic performance, but it can also have positive effects on the brain. Since surgery can lead to alterations in thinking, memory, and attention patterns in some patients, we will assess whether creatine can be protective against these changes in older adults undergoing surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurocognitive Disorders; Postoperative Delirium
• Intervention / Treatment: Dietary supplement: Creatine monohydrate

Detailed Description

Surgical interventions, while often necessary, are associated with substantial postoperative morbidity, particularly among older adults. Perioperative neurocognitive disorders (PND), characterized by changes in memory patterns in the perioperative period and are among the most common surgical complications in aging populations. Beyond their considerable economic burden, estimated to exceed $30 billion annually, PND impose profound immediate consequences for patients and caregivers and is associated with long-term adverse outcomes, including an increased risk of dementia. Despite their high prevalence and clinical impact, effective, scalable, and easily implementable preventive strategies for PND remain limited.

Creatine plays a critical role in supporting the brain's high metabolic demands, and its homeostasis may be disrupted during periods of physiological stress such as anesthesia and surgery. Creatine supplementation has demonstrated neuroprotective effects in other high-stress conditions. However, its potential to mitigate perioperative cognitive vulnerability has not been previously investigated. This study will evaluate creatine supplementation as a novel protective strategy to reduce the risk of PND in older adults undergoing surgery.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients scheduled for elective surgery under general anesthesia

Exclusion Criteria:

• History of creatine deficiency disorders
• Severe neurologic or psychiatric diseases
• History of stroke or head trauma
• Obesity (BMI ≥ 30 kg.m-²), kidney or liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients under creatine monohydrate intervention	Dietary supplement: Creatine monohydrate; Participants will receive creatine supplementation before surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative cognitive function assessed with the Montreal Cognitive Assessment (MoCA)	The MoCA is a validated tool to assess cognitive function. Scores range from 0-30, with higher scores representing better cognitive function	Within three weeks before surgery
Postoperative cognitive function assessed with the Montreal Cognitive Assessment (MoCA)	The MoCA is a validated tool to assess cognitive function. Scores range from 0-30, with higher scores representing better cognitive function	Within one month after surgery
Postoperative cognitive function assessed with the Montreal Cognitive Assessment (MoCA)	The MoCA is a validated tool to assess cognitive function. Scores range from 0-30, with higher scores representing better cognitive function	Within three months after surgery
Postoperative delirium assessed with the Confusion Assessment Method	The CAM is a validated tool to detect postoperative delirium	Up to 7 days after surgery

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Creatine; Perioperative Brain Health; Perioperative Neurocognitive Disorders
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Neurocognitive Disorders; Amino Acids, Peptides, and Proteins; Organic Chemicals; Amino Acids; Guanidines; Amidines; Creatine
• Other Study ID Numbers: 2025P002111

Drug and device information, study documents

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