Study setting

The study will be performed and the data will be collected and handled at the Sports Medicine department of the Gelderse Vallei Hospital in Ede, The Netherlands.

Eligibility criteria

In order to participate in this study, a participant must meet all of the following criteria: a clinical diagnosis of patellar tendinopathy based on a history of focal knee pain in patellar tendon or its patellar or tibial insertion in association with training and/or competition, palpation tenderness to the corresponding painful area (on the patellar tendon), and/or focal patellar tendon pain during patellar tendon loading with a pain provocation test (single leg decline squat and/or single leg jump squat, NB: imaging findings collected in this project will not be used as an eligibility criterion). Additional criteria are as follows: age 16–40 years old (the chosen age range will minimize chances of other conditions causing anterior knee pain such as osteoarthritis and osteochondrotic diseases like Sinding-Larsen-Johansson syndrome and Osgood-Schlatter disease), a current symptom duration of at least 12 weeks, sports participation at least once a week for at least 1 year before start of complaints, a VISA-P score < 80 out of 100 points, willingness to take (non-vegetarian) nutritional supplements, and willing and able to perform the PTLE program.

Athletes will be excluded if they have a known presence of inflammatory joint diseases (e.g., spondylarthropathy, gout, or rheumatoid arthritis) or familial hypercholesterolemia, if they underwent patellar tendon surgery, if they had a previous patellar tendon rupture of the index knee, if they suffer from acute knee injuries, including patellar tendon injuries with an acute onset, or if they show signs or symptoms of other coexisting knee pathology on physical examination (such as patellofemoral pain syndrome, joint effusion, and joint line tenderness), or if previously performed diagnostic imaging before the start of the study already showed other knee pathology (e.g., chondral lesion of the patella or trochlea on MRI or prepatellar bursitis on US). Athletes who use drugs with a putative effect on the patellar tendon in the preceding year (e.g., fluoroquinolones and statins); athletes who underwent local injection therapy with corticosteroids, other drugs, blood, platelet-rich plasma, or stem cells in the preceding 12 months; athletes who already participate in other concomitant treatment programs or research projects; athletes giving blood donation in a period of 2 months prior to each test day; athletes being pregnant or wish to become pregnant in the upcoming year; athletes who abuse hard drugs; athletes with an alcohol consumption > 21 units/week (men) or > 14 units/week (women); and athletes who already use hydrolyzed collagen supplementation will also be excluded.

Who will take informed consent?

The executive researcher will take informed consent. Information about patellar tendinopathy and the purposes and procedures of the study will be presented on a specifically designed website. Athletes with knee pain who are informed about the study will be contacted with regard to possible questions they might have before signing informed consent. After both the participant and the executive researcher have signed the consent, the participant will be asked to fill out an online questionnaire for an in- and exclusion criteria check. After digital screening, those who meet the inclusion criteria will be invited for a clinical screening examination by an experienced sports physician.

Additional consent provisions for collection and use of participant data and biological specimens

Additional blood samples will be obtained to be stored for use in future studies evaluating the pathobiology of PT. Information on the usage of blood samples is included in the current informed consent in order to specifically address the collection of these serum and plasma samples.

InterventionsExplanation for the choice of comparators

All participants will receive education and advice with regard to load management and criteria-based PTLE. The latter consists of 4 stages within the limits of pain according to the multidisciplinary Dutch guidelines for anterior knee pain [13] and, thus, is part of the usual care. PTLE has recently been proven to be superior to eccentric training [6]. Participants will follow this PTLE program until full recovery. This can be sooner than the 24-week intervention. In that case, participants will keep on performing maintenance exercises from the PTLE program.

In addition to the PTLE exercise program, participants will be randomly assigned to receive either the nutritional supplement hydrolyzed collagen/vitamin C (intervention) or a placebo supplement for 24 weeks. Even if full recovery is reached within the 24 weeks of intervention, participants will complete the 24 weeks of supplement usage.

Intervention description Hydrolyzed collagen + vitamin C versus placebo supplement

All participants will receive either a hydrolyzed collagen/vitamin C (intervention) supplement or a placebo supplement. The supplements will be taken per day for a duration of 24 weeks. Each day, the supplement will be taken 1 h before performing exercises from the PTLE program, or, when no exercises have to be performed, in the evening after dinner. The intervention supplement as well as the placebo are both produced by the company Rousselot BV (Ghent, Belgium). The intervention supplement contains 10 g of hydrolyzed collagen, in the form of collagen type I in combination with 40 mg vitamin C (48 kcal). The placebo supplement consists of 10 g maltodextrin (46 kcal). Both intervention and placebo powder are presented as sachets and the powder can be dissolved in cold water. The product is slightly sweetened to mask differences between intervention and placebo supplement.

PTLE (progressive tendon loading exercises)

All participants will receive criteria-based PTLE consisting of 4 stages within the limits of pain for 24 weeks. This intervention has recently been proven to be superior to eccentric training [6]. The program has been developed to be performed at the gym or in physical therapy practices. However, it has been modified so that participants can also perform the exercises at home, without equipment. The PTLE will be embedded in the usual care and is a method that is already implemented in many physical therapy practices. The exercise treatment will be explained to the participants by the executive researcher, together with physical therapists who received an explanation about the protocol before the study starts. In addition, the executive researcher will provide written information sheets and will provide a link to video instructions as part of the education. This includes an explanation of the condition, expected management, the positive influence of exercise therapy, and the positive effects of a gradual return to sports. Specific attention will be given to the relation between load and pain using the pain-monitoring model. Modification of all athletic activity (intensity, duration, frequency, and type of load) will be advised for activities that result in considerable patellar tendon pain, namely either significant reduction or even avoidance of the activity. We will stimulate the participants to perform (sports) activities within the limits of acceptable pain (VAS score ≤ 3 points on a scale 0–10, with 0 meaning no pain at all and 10 meaning unbearable pain).

The participants will need to follow an exercise program consisting of isometric (static), isotonic (dynamic), energy-storage (explosive), and sport-specific exercises consecutively, within the limits of acceptable pain [3]. Progression to each subsequent stage is defined using individualized progression criteria, based on the level of pain experienced during a pain provocation test that consists of one single-leg squat. If the VAS-score is 3 or less and exercises of the stage are performed for at least 1 week, progression to the next stage is advised.

Participants are instructed to gradually return to sport-specific training, performed every 2–3 days to allow for recovery from high tendon-loading exercises. In this stage, the isometric exercises of stage 1 will be continued on days that the sport-specific exercises are not performed. When all the exercises in stage 4 are performed within the limits of acceptable pain (VAS score ≤ 3 points), return to competition is recommended. Maintenance exercises are advised when return to play has been achieved. This includes isotonic exercises 3 times weekly and isometric exercises before training or competition.

As mentioned, the first instructions at the start of the intervention period will be given by the executive researcher and a physical therapist. After the elaborate instructions and explanations, participants will follow the exercise program, when possible under the guidance of a physical therapist, as part of their usual care program. Otherwise, the exercise program will be executed at a fitness center or at home. For all situations, instructional videos and an information brochure with explanations and pictures about the exercise program will be provided on a website. During the entire study period, a sports physical therapist with experience in tendon treatment will be available for participants when having questions.

The materials that are needed for home-based completion of these exercises (dynabands) will be offered to the participants after the instruction of the exercise program. The full PTLE program has been published elsewhere and is openly accessible [6].

Criteria for discontinuing or modifying allocated interventions

Participants can withdraw from the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a participant from the study for urgent medical reasons.

Since there are no further risks for participants in the study, there are no criteria for withdrawal of the participants based on any risk.

No adverse effects of hydrolyzed collagen or placebo are expected. Hydrolyzed collagen and maltodextrin are generally accepted as safe and have been used in this dosage and marketed in foods and dietary supplements globally for many years. In addition to the supplement, both groups are expected to experience improvement in symptoms as a result of the exercise therapy. In addition, the study has been designed to blend as much as possible with standard clinical care.

Strategies to improve adherence to interventions

Before the start of the intervention, participants will receive an elaborative explanation about the supplement and the exercise program. The explanation is also provided on the website, including short video clips with the exercises and a pdf containing all information about the exercise program.

Two factors will be monitored to keep track of study adherence: (1) compliance to the supplement intake (number of empty and unused supplement sachets brought by the participant and via the weekly questionnaire) and (2) compliance to the exercise program (total percentage of prescribed exercises performed (amount of load and number of series and repetitions will be monitored)). This will be asked on a weekly basis using a short online questionnaire. These questionnaires will be checked on a weekly basis. When the questionnaire is not filled out on the designated day, a reminder will be sent. With no response, a day later, participants will be called to remind them about the questionnaire.

Relevant concomitant care permitted or prohibited during the trial

Pain relieving medication should preferably not be used, but when participants experience pain with a VAS score of 7 or higher, with a duration of at least 24 h, the use of pain medication will be allowed. Preferably, participants should only use paracetamol (acetaminophen) as pain medication. Long-term use of NSAIDs is not allowed. All pain medication should be reported with the type of pain medication, dosage, date of intake, and reason of intake (e.g., knee pain or other causes of pain). No pain medication is allowed the day before and on the day of the tests. Participants have to report all use of co-interventions (patellar strap, inlays, pain medication, or other) in their weekly diary, as the use of pain-relieving therapies is a variable in this study.

Provisions for post-trial care

If participants still experience symptoms after completion of the study, we will advise them to contact the general practitioner for a referral to a sports medicine physician.

Outcomes Primary outcome measure VISA-P questionnaire

The primary outcome measure of the JUMPFOOD study is the change of the validated and disease-specific VISA-P score over 24 weeks, which will be compared between the supplement and placebo groups. This is a short questionnaire specifically designed for athletes with patellar tendinopathy measuring the severity of the injury by assessing pain, function, and ability to participate in sports activities [14]. A VISA-P score of 100 indicates no pain, maximum function, and maximum ability to play sports. The score decreases with increasing severity of symptoms of PT. The VISA-P questionnaire has been translated and validated in Dutch language [14]. The responsiveness of the VISA-P scale has recently been established in athletes with patellar tendinopathy. The minimum clinically important difference (MCID) of the VISA-P score was 13 points in that study [15].

Secondary outcome measures Body composition measurements

Body weight (kg), height (cm), and body fat percentage (%) using the sevenfold sum of skinfold will be measured.

Blood sampling

At all three test days (t = 0, t = 12, and t = 24 weeks), one blood sample will be drawn at baseline and one will be drawn 1 h after intake of the intervention or placebo supplement. At all test days, a sober blood sample will be drawn for the analysis of BSE and CRP which are general parameters for the determination of inflammation [16, 17]. At only the first test day, uric acid [18,19,20,21,22,23], cholesterol and lipid concentration [17, 24,25,26,27,28], Hb1Ac [26, 29, 30], thyroid-stimulating hormone (TSH), and free thyroxine (FT4) will be measured, since elevated levels are linked with a higher prevalence of tendon complaints, and thyroid hormones play a role in the etiology of tendinopathy [24, 25, 31].

At all three test days, at baseline and 1 h after intake of the supplement, a blood sample will be drawn to determine the specific N-terminal peptide of pro-collagen I (PINP) concentration change due to supplement intake and change over time to determine collagen build up in the body.

Functional tests Functional tests

Functional tests will be performed to determine the pain rating on a visual analogue scale (VAS) and to determine flexibility and strength. First, the participant has to perform a single leg decline squat where the participant performs a single leg squat to 60° of knee flexion on a 25° decline board. This test was designed to preferentially load the patellar tendon [32,33,34,35]. We record the VAS pain score after the first squat and after ten single-leg squats on the decline board. Isometric strength of the quadriceps, hamstrings, and abductors will be measured using the MicroFET (ProCare, Groningen, the Netherlands). Muscle length of the quadriceps and the hamstrings will be measured using a plurimeter. Also, a weight-bearing dorsiflexion lunge test will be performed to measure the angle of dorsiflexion using a plurimeter. Using the OptoGait (ProCare, Groningen, the Netherlands), we will measure ground reaction time during a drop jump test, we will measure the ratio between the tendon and muscle strength during a squat jump vs countermovement jump, and we will measure the difference and ratio between the left and right knee during hop tests (single, triple, medial side triple, 90° medial rotation and side hop test). Finally, a drift test will be performed to measure ground area deviation. All functional tests will first be performed on the contralateral side, followed by the affected side. If both sides are affected, the most affected side will be registered as affected side.

Imaging Imaging

Ultrasound (Hitachi Aloka Arietta 850 machine, with 18–5 Hz linear echo probe, in B mode 25 fps, in Doppler 19 fps, Tokyo, Japan) of the patellar tendon will be performed by an experienced musculoskeletal radiologist, or under the supervision of an experienced musculoskeletal radiologist. The participant will be examined in the supine position with the knees flexed for determining the structure and extended for determining vascularization. The ultrasound scan includes an assessment of patellar morphology and echogenicity and Power Doppler assessment (PDU) of the vascularity of the tendon. All mentioned aspects can be measured by performing one ultrasound per knee.

Ultrasound tissue characterization (UTC) of the patellar tendon will be used to determine 3D tendon integrity. Structure of the patellar tendon will be quantified using UTC. A standardized protocol will be used to take the UTC scans [36]. Participants will sit down on a treatment bench with the bench as much as possible in the popliteal fossa with approximately 90° knee flexion. An ultrasound probe (SmartProbe 12L5-V, Terason 2000 + ; Teratech) will be affixed to a tracking device (UTC Tracker, UTC Imaging) to standardize transducer tilt angle. The tracker device will move the probe automatically over the length of the tendon, capturing transverse images every 0.2 mm. The ultrasound probe in the tracking device will be placed perpendicular to the long axis of the tendon, moving from proximal to distal. Both patellar tendons will be scanned for each participant. All scans will be taken by a single examiner who is experienced with UTC. The consecutive transversal images will be used to create 3D reconstructions. The consistency of intensity and distribution of gray images will be calculated over a distance of 4.8 mm using UTC algorithms. Four echo types can be discriminated based on consistency, with echo type I representing the most stable pattern and echo type IV the least stable. Tendon structure will be quantified by calculating the percentages of these four echo types in multiple regions of interest (ROI) placed around the border of the tendon in the transverse view. ROIs will be selected at intervals no greater than 5 mm from the apex of the patella to 20 mm distally. Contours will be drawn every 5 mm and window size 17 will be used for imaging analysis. All tendons contours will be marked by trained personnel, due to practical implications. The inter- and intra-rater reliability of the processing of the scans is found to be excellent [37, 38].

Tendon stiffness

Patellar tendon stiffness will be assessed using myotonometric measurements with the MyotonPRO device (Myoton Ltd, Tallinn, Estonia). The measuring method of this device is based on the free oscillation technique. The following steps occur during a single measurement: (1) the device is placed perpendicular to the skin and a constant pre-pressure is applied for compressing the subcutaneous tissue; (2) a brief mechanical impulse is applied causing damped oscillation of the tissue; and (3) the co-oscillation generated in the tissue is recorded by an accelerometer. The myotonometer has good to excellent test–retest reliability and has been established in previous literature [39].

The anatomical landmark for the patellar tendon stiffness assessment will be the most painful spot in the patellar tendon but also 1 cm below the inferior pole of the patella and the midpoint of the patellar tendon. The participants will lie down on a treatment bench with their knees flexed to 90°, measured with a goniometer. In addition to stiffness measurements on the tendon, the stiffness of the rectus femoris muscle will be measured as well, at 1/3 and 2/3 of the muscle, with extended hip and knee. The myotonometric evaluation will be repeated 3 times per location. Only measures that have a coefficient of variation lower than 3% will be considered; otherwise, the measurement will be repeated.

For all imaging techniques and tendon stiffness measurements, the contralateral patellar tendon will also be examined for comparison. Here as well, if both sides are affected, the most affected side will be registered as the affected side.

Nutrition

A 3-Day Food Record (3DFR) will be recorded at the start and at the end of the intervention period by the use of the validated TRAQQ app of Wageningen University [40, 41]. Using this app, participants report what they have eaten for 3 days, after which the app automatically calculates the macro- and micronutrient intake. These 3 days will take place on two workdays and one weekend day. This will be measured to investigate their current nutritional status and potential causes or relationships between nutrition and the current tendon problems. Nutrients that will be measured are among others: protein and amino acid intake, total energy intake, alcohol consumption, and vitamin C intake. These nutrients were found to affect tendon health in a recent systematic review [42]. Amino acid intake is a more specific item that can be included by the use of the amino acid table that is part of the TRAQQ app and the Wageningen University. Here, the amino acid content of products is added to the Dutch food composition database. During the entire intervention period, participants will be asked not to radically change their diet. For example, changing to a vegan diet is not allowed during the study if this was not the participant’s habitual diet before the start of this study.

Questionnaires

Multiple questionnaires will be given at baseline, at 12 weeks, and at 24 weeks. These questionnaires involve general health and well-being (ED-5Q), central sensitization of pain (CSI), the influence of the participants’ injury on sports participation (OSTRC), categorizing subgroups within patients with PT (MSK), and a sports activity rating scale (SARS). In addition, a follow-up questionnaire will be given investigating subjective participant satisfaction with the PTLE program, the return to sports, the pain during activities of daily living, during sports and during the PTLE program, and investigating the use of co-interventions, training load, and the compliance to the supplement intake and PTLE program.

Other outcomes Weekly logbooks

Data on compliance to the training program, mean pain score during the exercises, and sport-specific training load will be registered on a weekly basis. The questionnaire will be automatically sent weekly as a reminder. In this online questionnaire, we ask the number of training days that week and the number of matches that week. We ask which percentage of the prescribed repetitions the participant had accomplished and the precise amount of load and number of series and repetitions of the exercise program executed. The training load that will be obtained from this questionnaire is defined as the total duration of training and matches played per week (minutes) multiplied by the experienced intensity of training sessions and games using the modified Borg CR-10 Rate of Perceived Exertion (RPE) scale [43]. In addition, we ask the level of pain when performing the exercises, and we ask for reasons why the participant has not performed the prescribed exercises. Answering options are (1) lack of time, (2) pain, (3) preferring sports activities, (4) rest day, and (5) lack of motivation. We ask whether the participant has returned to their sports level or not; answering options are (1) not active in sports, (2) no return to sports, (3) returning to sport but not in desired sport, (4) returning to desired sport but not at the preinjury level, and (5) returning to preinjury level in the desired sport. We ask how satisfied the participant is with the exercise program; answering options are (1) excellent, (2) good, (3) moderate, and (4) poor.

At the end of the study, participants will be asked whether they knew which of the two supplements they received during the intervention period. The results of the weekly questionnaire are stored using a secure data collection site where data can be accessed, submitted, and modified.

Participant timeline

Participants will be recruited from April 2023 until May 2025. Upon registration and signing informed consent, the executive researcher will screen participants for potential eligibility. To prevent participants from making an unnecessary visit to the hospital, the PI will ask among others the age, absence of known inflammatory diseases or hypercholesterolemia, previous knee conditions and treatments, use of medication, and participation in other treatment programs. To increase the likelihood of the diagnosis of patellar tendinopathy, we will use a self-administered pain map, where one of the six images shows the situation of PT. The potential participant will finally complete an online VISA-P questionnaire, which should be below 80 points to be eligible for the study. If these criteria are met, the participant is invited for inclusion measurements at the hospital Gelderse Vallei.

When the participant arrives at the hospital, further screening for inclusion criteria follows. A clinical examination will be performed by an experienced sports physician. The diagnosis will be based on clinical examination: focal pain at the inferior patellar pole or patellar tendon on palpation and a single-leg-decline squat. If the potential participant meets all the inclusion criteria, he/she is allocated to either intervention or placebo and invited for another appointment at the hospital for the baseline measurements. In addition, the 3DFR will be scheduled. This will be explained, which the participant fills in at home, using the app “TRAQQ” of Wageningen University.

At baseline, a test day will take place at hospital Gelderse Vallei, containing the outcome measures stated above (blood measurements, body composition measurements, questionnaires, imaging, stiffness measurements, and functional tests; see Fig. 1B and Table 1). At follow-up (12 and 24 weeks), the clinical, radiological, and blood parameters will be repeated. The measurements will be performed in an identical way as during the baseline measurements, with the exception of the ultrasound, which is only performed at baseline and at 24 weeks (see Fig. 1B). In addition, the 3DFR will be obtained at baseline and after 24 weeks, with no nutritional assessment at 12 weeks.

Table 1 Schematic diagram of the JUMPFOOD study

Tendinopathy-related symptoms will be recorded at baseline and 6, 12, 18, 24, and 52 weeks’ follow-up (Fig. 1A) using the VISA-P score. At 6, 18, and 52 weeks, this outcome measurement will be determined using a web-based form. The follow-up questionnaire that is given at baseline and 12 and 24 weeks is also given at 52 weeks of follow-up.

Sample size

The mean difference of change in VISA-P score over time between the intervention and placebo group is estimated to be 13 points higher in the intervention group compared to the placebo group. The standard deviation of the difference in VISA-P score is estimated to be 19 [15]. With a power estimated to be 80% and a significance level of 0.05, the sample size calculation (performed in G*Power 3.1.9.7) led to a total sample size of 70 participants. As we will compensate for an expected loss to follow-up of 9%, 76 participants will be included in total, i.e., 38 participants per treatment arm.

Recruitment

Dutch male and female athletes (age 16–40) suffering from anterior knee pain will be informed about the JUMPFOOD study via physical therapists, sports associations, clubs, and sport physicians. Coaches and clubs within the region of the study location are also informed about the study. Additionally, local, regional, and national publicity campaigns are used to draw attention to the study. For example, the Dutch volleyball association (NeVoBo), basketball association (NBB), handball association (NHV), korfball association (KNKV), and athletics association (Atletiekunie) will be informed about this study, and athletes will be informed through their websites and newsletters.