Collagen supplementation for tendon health
| ISRCTN | ISRCTN72255101 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72255101 |
| Secondary identifying numbers | NL84264.096.23 |
- Submission date
- 27/09/2023
- Registration date
- 06/10/2023
- Last edited
- 09/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Injury, Occupational Diseases, Poisoning
Plain English Summary
Background and study aims
Tendons transfer the force exerted by the corresponding muscle to bones and, therefore, are vital components of human locomotion. Tendon injury is very common, both in athletes and the general population. Once injured, tendons recover very poorly, resulting in a decrease in quality of life for the patient and a substantial burden on the health care system. Therefore, interventions that can aid in the prevention or treatment of tendon injury are warranted. The growth of all tissues, including tendons, is regulated by the net difference between protein synthesis and protein breakdown rates. Protein ingestion stimulates protein synthesis. Collagen is the main protein in human connective tissues, including tendons. The amino acids glycine and proline are the main building blocks of endogenous collagen and vitamin C serves as a co-factor in the synthesis and release of novel collagen proteins. Hence, dietary collagen may be the preferred protein source to deliver high amounts of glycine and proline and, together with vitamin C, maximize collagen synthesis in the tendon. However, no evidence is available on the effect of vitamin C-enriched collagen supplementation on human tendon protein synthesis. Hence, the main objective of the current study is to assess the impact of dietary collagen supplementation on human tendon protein synthesis.
Who can participate?
Adults aged between 18 and 40 years old attending the Department of Orthopedics from the participating hospital for planned anterior cruciate ligament (ACL) reconstruction with hamstring autograft
What does the study involve?
Participants need to ingest a test drink twice daily (100 mL per dose), perform 5 minutes of low-intensity exercise twice daily, ingest deuterium oxide (20 mL) daily, and provide a saliva sample daily, for seven days.
What are the possible benefits and risks of participating?
Benefits not provided at time of registration. The burden and risks involved in participating in this experiment are limited. The ingestion of deuterium oxide has been applied in numerous published studies and is entirely safe and non-toxic in the amounts provided in the present study. Tissue collection will occur during ACL surgery, which is already planned as part of the participants’ course of treatment. A graft of the hamstring tendon will be used for ACL reconstruction, and a sample will be obtained under anesthesia during the standard surgical procedure. The tissue is extracted during the standard procedure, meaning that patients will not take on any extra burden by participating in this study. Two additional blood samples (2 x 10 mL) will be obtained before and after the experimental period.
Where is the study run from?
HAN University of Applied Sciences (The Netherlands)
When is the study starting and how long is it expected to run for?
February 2023 to July 2026
Who is funding the study?
HAN University of Applied Sciences (The Netherlands)
Who is the main contact?
Dr Jan-Willem van Dijk, JanWillem.vanDijk@han.nl (The Netherlands)
Contact information
Public, Scientific, Principal Investigator
School of Sport and Exercise
HAN University of Applied Sciences
PO Box 6960
Nijmegen
6503 GL
Netherlands
 ORCID ID |
0000-0001-9674-1505 |
|---|---|
| Phone | +31 024 353 0500 |
| JanWillem.vanDijk@han.nl |
Study information
| Study design | Double-blind randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | The effect of collagen supplementation on human tendon protein synthesis |
| Study acronym | COL-TEN |
| Study hypothesis | The main objective of the current study is to assess the impact of dietary collagen supplementation on human tendon protein synthesis. |
| Ethics approval(s) |
Approved 30/05/2023, Medical Ethical Review Commission METC Zuyderland (Secretariaat, T3 Heerlen, Postbus 5500, Sittard, 6130 MB, Netherlands; +31 (0)88 4590129; metc@zuyderland.nl), ref: METCZ20230038 |
| Condition | Tendon protein synthesis in otherwise healthy males and females scheduled for anterior cruciate ligament (ACL) surgery. |
| Intervention | The study involves two parallel groups: an intervention group and a control group: Intervention: A vitamin C-containing collagen supplement (20 g per dose) will be ingested as a drink (100 mL of water mixed with 20 g of collagen powder) twice daily for 7 days, once at breakfast and once before sleep. Control: A vitamin C-enriched maltodextrin will be used as an isocaloric placebo. Using a computer random number generator, participants will be randomly allocated to the intervention group or the placebo group on a 1:1 ratio, stratified by sex. This study has a double-blind design, with both participants and researchers blinded to treatment allocation. A member of our research group will create the randomization list. The intervention providers are an experienced lab technician with a background in chemistry and a researcher with a background in human movement sciences. The intervention is a food-grade supplement which will be provided to the participant by the researcher. Vitamin C-enriched collagen or maltodextrin supplementation will be administered at a twice daily dose of 20 g (40 g per day), as an oral supplement of 100 ml per drink. The participant mixes the dose of powder with tap water at home. After stirring the mixture for 10 seconds, the participant drinks the mixture. Intervention occurs at the participant's home. Surgery will occur in the hospital. Participants will be visited once at their home for baseline measurements. The second study visit will take place at the hospital before surgery. |
| Intervention type | Supplement |
| Primary outcome measure | Tendon tissue protein synthesis rate, expressed as fractional synthesis rate (FSR, %/d), will be measured for 7 days prior to surgery. To calculate FSR, the standard precursor-product method will be used. Tendon protein synthesis rates will be calculated from: 1. Saliva 2H enrichment (i.e., precursor) 2. Tissue protein-bound enrichment 2H-alanine 3. Plasma albumin enrichment 2H-alanine |
| Secondary outcome measures | A ligament in muscle protein synthesis rate, expressed as fractional synthesis rate (FSR, %/d), will be measured for 7 days prior to surgery. To calculate FSR, the standard precursor-product method will be used. Tendon protein synthesis rates will be calculated from: 1. Saliva 2H enrichment (i.e., precursor) 2. Tissue protein-bound enrichment 2H-alanine 3. Plasma albumin enrichment 2H-alanine |
| Overall study start date | 01/02/2023 |
| Overall study end date | 01/07/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 40 Years |
| Sex | Both |
| Target number of participants | 30 |
| Participant inclusion criteria | 1. Otherwise healthy male and female volunteers 2. Aged 18 to 40 years old 3. Recruited from patients attending the Department of Orthopedics from the participating hospital 4. Planned for ACL reconstruction with hamstring autograft 5. BMI ≥18.5 and ≤27.5 kg/m2 |
| Participant exclusion criteria | 1. Blood donation during the study period or during the last 2 months 2. Pregnancy 3. Third-generation oral contraceptives 4. Currently smoking 5. Consumption of >21 alcoholic beverages per week 6. Use of any medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescribed acne medications) 7. Regular use of protein or other nutritional supplements (including vitamins). 8. Reported slimming or medically prescribed diet 9. Use of antibiotics in the past month 10. Current participation in another biomedical research study |
| Recruitment start date | 28/02/2024 |
| Recruitment end date | 01/06/2026 |
Locations
Countries of recruitment
- Netherlands
Study participating centres
Nijmegen
6525 AJ
Netherlands
Eindhoven
5631 BM
Netherlands
Sponsor information
University/education
PO Box 6960
Nijmegen
6503 GL
Netherlands
| Phone | +31 (0)24 353 0500 |
|---|---|
| info.asb@han.nl | |
| Website | https://www.hanuniversity.com/en/# |
"ROR" |
https://ror.org/0500gea42 |
Funders
Funder type
University/education
No information available
Results and Publications
| Intention to publish date | 01/07/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request. Upon reasonable request by other researchers, raw data (Excel file) will be made available after the publication of the scientific reports. Data can be used for scientific peer review or meta-analytic procedures. Data will be fully anonymized. Access to the datasets is via JanWillem.vanDijk@han.nl. |
Editorial Notes
09/04/2025: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2025 to 01/06/2026.
2. The overall end date was changed from 01/07/2025 to 01/07/2026.
3. The plain English summary was updated to reflect these changes.
01/03/2024: The recruitment start date was changed from 09/10/2023 to 28/02/2024.
09/10/2023: Internal review.
03/10/2023: Study's existence confirmed by Medical Ethical Review Commission METC Zuyderland (Netherlands)
