Creatine Monohydrate for Mild Traumatic Brain Injury: a Randomised Controlled Pilot Study

NCT06644131 | Completed

• 1 other identifier: 11.651
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: Approximately one-third of patients with concussion experience persistent symptoms that, in addition to causing serious discomfort, may lead to unemployment and other socioeconomic challenges. Animal studies suggest that creatine monohydrate may alleviate post-concussive symptoms. This pilot study investigated the effects of creatine monohydrate on post-concussive symptoms in humans and assessed the feasibility of the pilot trial. Design: Three-arm randomised controlled pilot trial (intervention, placebo, control). Setting: Participants were recruited through neurological outpatient clinics and public outreach in Denmark. Participants: The study included 34 participants aged 20-45 years who had been experiencing persistent post-concussive symptoms for 6-18 months since injury. Participants were randomised to one of three groups. Intervention: The intervention group received 5 g of creatine monohydrate daily for seven weeks. The placebo group received an identical inert powder following the same regimen. The control group received usual care only. Primary and secondary outcome measures: The primary outcome was post-concussion symptoms (Rivermead Post Concussion Symptoms Questionnaire (RPQ)). Secondary outcomes were acute (RPQ-3) and persistent (RPQ-13) symptoms, assessed at three time points (week 0, 4 and 8). Results: All participants completed follow-up, indicating the trial's high feasibility and practicality. The intervention group did not significantly differ from the placebo or control groups. Moderate effect sizes were noted for RPQ-13 and total RPQ scores (d = -0.47, -0.46) and small for RPQ-3 scores (d = -0.22), although none reached statistical significance. Similar effects were observed between the placebo and control groups. Conclusions: The study showed strong usability and practical feasibility. Effect sizes were exploratory and not indicative as evidence of treatment efficacy at this stage. Larger randomized controlled trials are needed to determine whether creatine monohydrate could be a safe, accessible adjunctive treatment for post-concussive symptoms.

Conditions

Mild Traumatic Brain Injury; Concussion (Diagnosis)

Keywords

Concussion; Mild traumatic brain injury; Creatine Monohydrate; Persistent post-concussive symptoms

Outcome Measures

Primary Outcomes (1)

• Change from baseline post-concussion symptoms at 7 weeks

  Rivermead post-concussion symptom questionnaire (16 items). The responses are scored on a ordinal rating system from 0 - 4, where 0 = never experienced at all, 1 = no more of a problem, 2 = a mild problem, 3 = a moderate problem, and 4 = a severe problem. Scoring 0-64. Scoring 64 is the maximum value. Decrease in value over time is associated with improvement or lower severity.

  Baseline, 3 weeks and 7 weeks.

Secondary Outcomes (1)

• Change from baseline body weight at 7 weeks

  Baseline, 3 weeks and 7 weeks.

Other Outcomes (3)

• Change in height from baseline to 7 weeks

  Baseline

• Level of training status at baseline

  Baseline

• History with persistent post-concussive symptoms (PCSS) (baseline)

  Baseline

Study Arms (3)

Intervention group (Creatine)

EXPERIMENTAL

Creatine Monohydrate administered once a day for seven weeks - with 5 g/day for the entire period.

Dietary Supplement: Creatine Monohydrate

Control group - No treatment

NO INTERVENTION

The control group will receive standard care. However, to our knowledge there is no common accepted description of standard care in the literature. In general, these participants will be advised to keep as asymptomatic as possible throughout seven weeks, and live as normal as possible.

Placebo group (Sugar pill)

PLACEBO COMPARATOR

Powdered sugar administered once a day for seven weeks - with 5 gram/day for the entire period.

Dietary Supplement: Sugar Pill (Placebo)

Interventions

Creatine Monohydrate DIETARY_SUPPLEMENT

Creatine Monohydrate

Intervention group (Creatine)

Sugar Pill (Placebo) DIETARY_SUPPLEMENT

Placebo - sugar pill

Placebo group (Sugar pill)

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The time since concussion was 6-18 months.
• The age range was 20-45 years.

You may not qualify if:

• Moderat to high level of intensity for no more than 10 hours per week
• Pregnant

Sponsors & Collaborators

• University of Southern Denmark: lead

Study Sites (1)

University of southern Denmark

Odense, 5230, Denmark

Location

Related Links

• Related Info

MeSH Terms

Conditions

Brain Concussion; Disease

Interventions

Creatine; Sugars

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Carbohydrates

Study Officials

• Michael Marcussen, Associate Professor

  University of Southern Denmark (SDU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single (Participant)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 16, 2024
• Study Start: August 1, 2023
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available beginning 9 to 36 months following publication of the primary results. The IPD will be accessible for a period of 5 years following its initial availability.
• Access Criteria: Access will be granted to qualified researchers affiliated with academic, clinical, or regulatory institutions. Requests must be accompanied by a research proposal approved by an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable. Researchers must enter into a data use/sharing agreement with the data custodian (Commotio Danmark and the University of Southern Denmark). Data will be provided in a secure format following approval.

Locations

DK (1)