Creatine and Perioperative Brain Health (CREATE)

Creatine Intervention in Older Adults to Improve Perioperative Brain Health

The overall goal of this study is to evaluate the feasibility of perioperative oral creatine supplementation and to explore its effects on cognitive function and physiological responses to surgery in older adults. Creatine is commonly used to enhance athletic performance, but it can also have positive effects on the brain. Since surgery can alter thinking, memory, and attention patterns in some patients, we will assess whether creatine affects these changes in older adults undergoing surgery.

Study Overview

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

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, are among the most common surgical complications in aging populations. Beyond their considerable economic burden, estimated to exceed $30 billion annually, PND imposes 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 been demonstrated to be neuroprotective in high-stress conditions. However, the potential effects of creatine during perioperative cognitive vulnerability have not been previously investigated. This study will evaluate the feasibility of creatine supplementation in the perioperative period and explore its effects on cognitive function and physiological responses to surgery in older adults.

• Study Type: Interventional
• Enrollment (Estimated): 120
• 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
• Renal or neurodegenerative disorders
• History of stroke or significant head trauma, presence of intracranial mass lesions
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Creatine group; Patients in the creatine group will be instructed to take approximately 20g of creatine monohydrate daily for one week, followed by a maintenance phase of approximately 5g per day	Dietary supplement: Creatine monohydrate; Participants will receive creatine supplementation before surgery
Placebo Comparator: Placebo group; Placebo group patients will be instructed to take a placebo following the same regimen as the creatine group.	Other: Placebo; Participants in the placebo group will receive an identical placebo 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 (CAM)	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): September 1, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): August 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): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 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