Creatine for Concussion

(CSCR Trial)

Overseen By Michelle Weber Rawlins, PhD, ATC

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: San Diego State University

Must not be taking: Creatine

Disqualifiers: Learning disability, Renal disease, Migraine, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Variable (up to 100 weeks)

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if creatine, a dietary supplement, helps speed up recovery from concussions. Participants will either add creatine to their diet or maintain their usual diet after a concussion. Researchers will compare the time it takes for participants to become symptom-free and assess their mental and physical recovery. The trial is suitable for individuals aged 18-35 with a recent concussion and no history of migraines or certain medical conditions. As an unphased trial, it offers a unique opportunity to contribute to understanding concussion recovery and potentially benefit from creatine supplementation.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using creatine or have used it in the past 6 weeks.

Is there any evidence suggesting that creatine supplementation is likely to be safe for humans?

Research has shown that creatine is generally safe for most people. For over 25 years, studies have examined its safety, finding that creatine supplements rarely cause serious side effects. Some individuals might experience minor issues like stomach upset or muscle cramps, but these are uncommon.

Creatine is a popular supplement, often used by athletes to enhance performance. Its widespread use with few reported problems supports the evidence of its safety for most people. Additionally, research on creatine for mild traumatic brain injuries, such as concussions, suggests it might aid recovery without causing harm.

In summary, creatine has a strong safety record, making it a low-risk option for those considering joining a trial for concussion recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Creatine supplementation is unique because it uses creatine, a natural compound typically involved in energy production in the body. Unlike standard concussion treatments that focus on symptom management or rest, creatine might help by providing extra energy support to the brain, potentially speeding up recovery. Researchers are excited about creatine because it could offer a more proactive approach by directly supporting brain cell energy levels during the healing process.

What evidence suggests that creatine might be an effective treatment for concussion?

Research has shown that creatine might aid recovery from a mild traumatic brain injury (mTBI), such as a concussion. It may protect the brain by boosting energy levels in brain cells, potentially reducing injury symptoms. Some studies suggest that creatine supplementation could improve symptoms and speed up recovery after a concussion. In this trial, participants in the creatine supplementation arm will consume creatine alongside their usual diet. Creatine is thought to enhance brain function, helping to reduce the severity and duration of symptoms. While more research is needed to confirm these benefits, early results appear promising. ^{1 2 3 5 6}

Who Is on the Research Team?

Michelle Weber Rawlins

Principal Investigator

San Diego State University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-35 who have been diagnosed with a concussion within the last 72 hours. It's not suitable for those outside this age range or if more time has passed since their injury.

Inclusion Criteria

I am between 18 and 35 years old and was diagnosed with a concussion in the last 3 days.

Exclusion Criteria

History of learning disability

I am currently using creatine or have not used it in the last 6 weeks.

I have a history of mental health issues or migraines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Initial Assessment and Randomization

Participants are assessed using SCOAT-6 and demographic questionnaire, and then randomly assigned to creatine supplementation or control group

1 week

1 visit (in-person)

Treatment

Intervention group consumes creatine daily until asymptomatic; control group follows usual diet

Variable (up to 100 weeks)

Regular contact (frequency varies based on recovery)

Asymptomatic Assessment

Once asymptomatic, participants undergo SCOAT-6, CNS Vital Signs, and King-Devick assessments

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for any recurrence of symptoms and overall recovery

4 weeks

1-2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Creatine

Trial Overview The study is testing whether taking creatine helps people recover from concussions faster and improves their brain function outcomes compared to those not taking it. Participants' recovery times and cognitive functions will be measured and compared.

How Is the Trial Designed?

Group I: Creatine supplementation Experimental Treatment 1 Intervention

The intervention group will consume their usual diet plus 5 grams of creatine for the first four days following the initial meeting, and then 3 grams of creatine once per day thereafter until asymptomatic.

Group II: Control Group Active Control 1 Intervention

Participants will consume their normal daily diet.

Creatine is already approved in United States, European Union for the following indications:

Approved in United States as Creatine Monohydrate for:

• Dietary supplement for muscle growth and performance
• Potential treatment for post-concussive symptoms

Approved in European Union as Creatine Monohydrate for:

• Dietary supplement for muscle growth and performance
• Potential treatment for post-concussive symptoms

Who Is Running the Clinical Trial?

San Diego State University

Lead Sponsor

Trials

182

Recruited

119,000+

Published Research Related to This Trial

Creatine monohydrate (CrM) remains the only form of creatine with substantial evidence supporting its bioavailability, efficacy, and safety, as confirmed by a review of various marketed creatine forms.

Despite ongoing claims about other 'novel forms' of creatine, many lack sufficient evidence for effectiveness and safety, and CrM is still the recommended source by professional organizations and regulatory authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. Kreider, RB., Jäger, R., Purpura, M.[2022]

Creatine monohydrate is effective for enhancing performance in high-intensity, short-duration activities, supported by a large body of research involving both acute (20 g/d) and chronic (3-5 g/d) supplementation studies.

The Observed Safe Level (OSL) for chronic creatine supplementation is established at 5 g/d, indicating strong safety evidence at this dosage, while higher intakes lack sufficient long-term safety data despite being tested without adverse effects in acute studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. Shao, A., Hathcock, JN.[2013]

Creatine monohydrate (CM) has an oral bioavailability of 53% at a low dose (10 mg/kg) but drops to only 16% at a high dose (70 mg/kg), indicating that the effectiveness of CM can vary significantly with dosage.

In comparison, creatine hydrochloride (CHCL) shows improved solubility and a higher predicted oral bioavailability of 66% at the same high dose, suggesting that alternative formulations of creatine could enhance absorption and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth. Alraddadi, EA., Lillico, R., Vennerstrom, JL., et al.[2020]

In a study of 134 patients undergoing coronary artery bypass graft surgery (CABG), L-carnitine administration significantly reduced the incidence of postoperative atrial fibrillation (AF) from 19.4% in the control group to 7.5% in the L-carnitine group.

L-carnitine also lowered postoperative C-reactive protein (CRP) levels, an inflammation marker, indicating that it may help reduce inflammation associated with AF after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation. Dastan, F., Talasaz, AH., Mojtahedzadeh, M., et al.[2018]

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with some minor side effects like gastrointestinal issues and muscle cramps reported.

While most creatine forms are unlikely to pose safety concerns, there are specific safety concerns associated with creatine orotate, creatine phosphate, and magnesium creatine chelate, indicating that not all creatine supplements are equally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. Andres, S., Ziegenhagen, R., Trefflich, I., et al.[2018]

In a study of 198 acute stroke patients undergoing contrast-enhanced CT imaging, only 2.9% developed contrast-induced nephropathy (CIN), indicating a low risk of kidney damage associated with this imaging technique.

None of the patients developed chronic kidney disease or required dialysis, suggesting that prompt multimodal CT imaging can be safely performed even when baseline kidney function is unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke. Hopyan, JJ., Gladstone, DJ., Mallia, G., et al.[2021]

A short 1-hour hydration protocol using sodium bicarbonate (3 ml/kg/h) is as effective as the conventional 24-hour saline hydration (1 ml/kg/h) in preventing kidney function decline in patients with impaired renal function undergoing computed tomography angiography (CTA) before transcatheter aortic valve implantation (TAVI).

No cases of contrast-induced acute kidney injury (CI-AKI) or the need for dialysis were observed in either hydration group, indicating that both methods are safe for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short versus conventional hydration for prevention of kidney injury during pre-TAVI computed tomography angiography. van Mourik, MS., van Kesteren, F., Planken, RN., et al.[2023]

In a study of 158 patients with renal impairment who received gadolinium-based contrast media (Gd-CM) for MRI or MRA, 16.5% developed gadolinium-induced acute kidney injury (Gd-AKI).

Sepsis was identified as a significant independent risk factor for developing Gd-AKI, highlighting the need for careful monitoring of renal function in high-risk patients after Gd-CM administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of acute kidney injury after exposure to gadolinium-based contrast in patients with renal impairment. Chien, CC., Wang, HY., Wang, JJ., et al.[2013]

This study aims to evaluate the effectiveness of creatine monohydrate (CrM) in treating persistent post-concussive symptoms (PPCS) in individuals aged 25-35 who have experienced these symptoms for 6-12 months, using a double-blinded randomized controlled trial design over a 7-week period.

The primary outcome will be measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), with the study approved by ethical committees, highlighting its commitment to safety and rigorous scientific standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study protocol of a randomized controlled trial for the potential effects of creatine monohydrate on persistent post-concussive symptoms. Bødker, RL., Marcussen, M.[2023]

In a study involving 40 rats, l-carnitine significantly improved kidney function by reducing serum creatinine and blood urea nitrogen levels, indicating its potential efficacy in protecting against contrast media-induced nephrotoxicity.

L-carnitine treatment also decreased levels of proinflammatory cytokines and apoptosis markers, suggesting it helps restore the oxidant/antioxidant balance and reduces kidney damage in cases of nephrotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis. Kunak, CS., Ugan, RA., Cadirci, E., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6094347/

Creatine Supplementation After Mild Traumatic Brain Injury This review investigates the potential for creatine supplementation following mild traumatic brain injury (mTBI), as well as potential neuroprotective effects ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06644131

Effect of Creatine Monohydrate on Persistent Post ... The primary outcome of the study is changes in RPQ score. Changes in weight and training status will be adjusted for as potential confounders. Detailed ...

3. health.mil health.mil/Reference-Center/Publications/2025/09/25/TBICoE-Information-Paper-on-Creatine-and-TBI

Information Paper on Creatine and TBI 23 Increasing the availability of creatine in tissue may enhance cellular metabolism and thereby reduce the severity of injury-related symptoms.

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1209548/full

Pilot study protocol of a randomized controlled trial for the ... The aim of this study is to examine the effect of CrM on PPCS assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ).

5. tandfonline.com tandfonline.com/doi/abs/10.1080/15502783.2025.2533681

Neuroprotective effects of creatine supplementation in mild ... Neuroprotective effects of creatine supplementation in mild TBI ... traumatic brain injury” OR “repetitive head impact”). Quantitative ...

6. gssiweb.org gssiweb.org/en/sports-science-exchange/Article/the-safety-and-efficacy-of-creatine-monohydrate-supplementation-what-we-have-learned-from-the-past-25-years-of-research

THE SAFETY AND EFFICACY OF CREATINE ... There is the potential that creatine monohydrate supplementation may reduce the severity or decrease the duration of mild traumatic brain injury (mTBI, ...