The Effect of Creatine Monohydrate on Persistent Post-concussive Symptoms

July 11, 2024 updated by: Michael Haurum Marcussen, Psychiatric Research Unit, Region Zealand, Denmark

The Effect of Creatine Monohydrate on Persistent Post-concussive Symptoms - a Pilot Study Protocol

The purpose of this study, is to investigate whether creatine monohydrate as a supplement reduces the number and severity of symptoms in patients with persistent post-concussive symptoms through self-reported post-concussion symptoms questionnaires.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Mild traumatic brain injury (mTBI), which throughout the literature is used interchangeably with concussion, is a problem of public concern. It is estimated that between 0.6 % and 1.2 % of the general population will suffer an mTBI each year which equals to 48-96 millions of people on a world scale. Out of these, an estimated 10-30 % of the patients, will suffer from persistent PPCS. These symptoms typically includes headache, poor concentration, memory problems, fatigue, sleep difficulties, dizziness, irritability, feeling nervous or anxious. PPCS has proven to be not only a health problem, but also a socioeconomical problem. Data has showed that salary in Denmark five years after a concussion decreased 4.2 %, with an increased risk of losing ones job. At the moment no single treatment option is available with guaranteed success, and therefore nutritional supplements are a possibility.

The nutritional supplement CrM is one of the most popular ergogenic aids on the market among professional and amateur athletes. It is mostly used in the development of muscle mass, as creatine is primarily located skeletal muscle. Roughly five percent of the body's creatine is distributed in the brain and testicles. As mTBI's also see a change in the metabolism of the brain, creatine supplementation might be beneficial for patients with PPCS. This is further supported by a newly conducted study, that creatine supplementation may reduce the severity of mild concussion in animal models.

Furthermore, as the enzyme Creatine Kinease (CK), which is involved in ATP energy system, also has a brain specific isoform (BB-CK), creatine may be a relevant part of the energy system of the central nervous system (CNS). In addition evidence points towards creatine supplementation can increase cellular energy availability. It has been reported to increase brain phosphocreatine content by as much as 15 %, which in turn improves the metabolic processes of the brain.

CrM has been described to be a potent anti-inflammatory molecule. It has been shown to reduce the cytotoxic effects in oxidatively-injured cells without affecting antioxidant enzyme activities, and has been shown to inhibit reactive oxygen species-induced formation of mitochondrial permeability transition pores in the liver mitochondria of mice. At the same time, concussion seems to increase inflammation in the brain, and this inflammation has been hypothesized to correlate with the symptomatology and duration. And even though research in the area of recovery is still scarce, neuroinflammation seems to play a vital role in the pathophysiology of concussions. This warrants hopes of a decrease in post-concussive symptoms.

Other studies have indicated an improvement of cognitive functions, including fatigue, working memory and mood state. All symptoms related to PPCS. Additionally evidence points towards creatine supplementation can help with chronic fatigue, depression and anxiety. All this points towards CrM being helpful in the treatment of PPCS.

Currently there is not viable treatment option for these patients, but if the intervention shows positive results, patients suffering from PPCS would be able to improve on their symptoms, relatively easy and cheap. They would have a go-to supplement, that would make it possible for them to get a normal day, without any of the symptoms connected to PPCS.

The pilot study will be performed as a randomized controlled trial in accordance with the Spirit Guidelines. The study is expected to include a convenience sample of 45 patients. The patients will randomly be allocated to either a control group, placebo group or intervention group, with 15 patients in each. The study will be double blinded, i.e., the participants and personel not knowing which group the patients will be allocated to. Furthermore, the process of randomization will consist of a nutritionist not otherwise associated with the study, randomly allocating each participant in a group, until sample size is reached. The person in charge of this, will also be distributing either the placebo or the CrM to the participants in each of these groups.

CG will not receive any treatment other than usual treatment. PLA and INT will both receive a powder, that has to be ingested. PLA will receive a powder similar in looks to CrM, but with no apparent nutritional value, while INT will receive CrM.

As both PLA and INT are the interventions, they will follow the same protocol for ingestion: 5 grams pr day in seven weeks. All 5 grams will be ingested at once. This protocol has been chosen instead of the more common 0.3 g/day for the first week, ingested over five times during the day. In other studies on CrM and the brain, this have been the chosen strategy also. But studies on CrM in the muscles show, that both protocols illicit the same response with 28 days, and the loading phase is not required. Furthermore, some studies have used this protocol with creatine supplementation, and found increased cognitive function. Our reason for choosing 5 g/day in seven weeks, is to increase the chances of compliance, and decrease the risks of discomfort with to high an intake of CrM. An intake five times a day for the first week, is demanding, and will most likely get some participants to quit the study.

At the mid phase of the study, all baseline measurements will be done again. The length of the intervention is seven weeks. After the seven weeks, all baseline measurements will be done again. And a week after last ingestion, the measurements will be done one last time. At the week eight appointment, every participant will have to answer whether they thought they were getting placebo or CrM. This is done in order to figure out how big an effect placebo have on the results.

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

The study population will be patients with persistent post-concussive symptoms between six and twelve months at start of participation. Participants will be recruited through social media and fourteen neurological outpatient clinics located in Denmark. At the start of the study, participants will have to be between 25 and 35 years of age. This will make the population a homogenous age group, and we will avoid physical and cognitive challenges related to early childhood and adolescents, as well as avoiding the degeneration in physical capacities that begin at approximately the age of 35, as well as the cognitive decline around the same time.

The anthropometrics of the participants will consist of age (years), gender (male/female), height (cm), bodymass (kg), period with PPCS (months), concussion history (yes/no), if yes, then how many (number), and training status (hours/week).

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Odense, Denmark, 5239
        • Recruiting
        • University of Southern Denmark
        • Contact:
        • Sub-Investigator:
          • Ronni Lykke Bødker, M.Sc.
        • Principal Investigator:
          • Michael H Marcussen, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 31 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have had PPCS for a minimum of six months and a maximum of 18 months at the start of the study.
  • Being between 20 and 45 years of age

Exclusion Criteria:

  • Elite athletes, as well as people who in general is physical active, at an intensity of moderat to high, for more than ten hours a week on average.
  • Participation in other interventions/treatment that could affect this study
  • Have had PPCS in:
  • =<6 months
  • =>18 months
  • Pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group
Creatine monohydrate administered once a day for seven weeks - with 5 g/day for the entire period.
Dietary supplement: Creatine Monohydrate
Follows
No Intervention: Control group
The control group will receive standard care. However, to our knowledge there is no common accepted description of a standard care in the literature. In general, these participants will be advised to keep themselves as asymptomatic as possible throughout the entire seven weeks, and besides that live as normal a life as they can.
Placebo Comparator: Placebo
Powdered Sugar administered once a day for seven weeks - with 5g/day for the entire period.
Dietary supplement: Creatine Monohydrate
Follows

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline Post-Concussion Symptoms at 7 weeks
Time Frame: Baseline, 3 weeks and 7 weeks (follow-up)
Rivermead Post-Concussion Symptom Questionnaire
Baseline, 3 weeks and 7 weeks (follow-up)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline Body weight at 7 weeks
Time Frame: Baseline, 3 weeks and 7 weeks (follow-up)
As we are using a dietary supplement as our intervention, following participants body weight in kg throughout the intervention is necessary in order to know if changes in body weight have any effect on our results.
Baseline, 3 weeks and 7 weeks (follow-up)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Height
Time Frame: Baseline
Descriptive measurement
Baseline
Training status
Time Frame: Baseline
To determine if the participants are at the same initial training status.
Baseline
Period with PPCS
Time Frame: Baseline
To assess persistent post-concussive symptoms
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Psychiatric Research Unit, Region Zealand, Denmark

Collaborators

University of Southern Denmark

Investigators

  • Principal Investigator: Michael Marcussen, Dr., University of Southern Denmark (SDU), Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

September 14, 2022

First Submitted That Met QC Criteria

September 27, 2022

First Posted (Actual)

September 30, 2022

Study Record Updates

Last Update Posted (Actual)

July 12, 2024

Last Update Submitted That Met QC Criteria

July 11, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRURegionZealand4

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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