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

Trial Summary

What is the purpose of this trial?

The proposed study aims to compare concussion recovery in those supplementing creatine and those not supplementing creatine. Specific aim 1: To compare number of days until asymptomatic between those taking creatine vs. those not taking creatine following a concussion. Hypothesis: The investigators hypothesize that individuals taking creatine will become asymptomatic sooner than those not taking creatine.Specific aim 2: To compare typical concussion assessment scores (i.e., symptom score, mental status, neurocognition, balance, motor coordination, and visual performance) between those taking creatine vs those not taking creatine following a concussion once asymptomatic.Hypothesis: The investigators hypothesize that individuals taking creatine will have better symptom scores, balance, mental status, and neurocognition assessment scores than those not taking creatine once asymptomatic. The investigators will calculate descriptive statistics for all demographic, days to asymptomatic, and concussion assessments. For specific aim 1, The investigators will calculate a t-test to determine if days to asymptomatic differed in those taking creatine vs. those not taking creatine. For specific aim 2, the investigators will calculate t-tests with Bonferonni corrections to determine if concussion assessment scores (Sport Concussion Office Assessment Tool-6 assessments, CNS Vital Signs, visual assessment) differed in those taking creatine vs. those not taking creatine.

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 creatine safe for human use?

There is no specific safety data on creatine for concussions in the provided research articles, but creatine is generally considered safe for human use when taken in recommended doses. It has been widely used as a dietary supplement, particularly among athletes, with few reported side effects. ^{1 2 3 4 5}

How does creatine monohydrate differ from other treatments for concussion?

Creatine monohydrate is unique because it has shown potential to improve cognitive function, chronic fatigue, depression, and anxiety in people with persistent post-concussive symptoms, while no single treatment currently guarantees success for concussion recovery. Additionally, creatine monohydrate is well-studied for its safety and efficacy, making it a reliable option compared to other less-researched forms of creatine. ^{6 7 8 9 10}

Research Team

Michelle Weber Rawlins

Principal Investigator

San Diego State University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Short versus conventional hydration for prevention of kidney injury during pre-TAVI computed tomography angiography. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Risk of acute kidney injury after exposure to gadolinium-based contrast in patients with renal impairment. [2013]

5. England 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. [2018]

6. Switzerland 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. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth. [2020]