Is Retinyl Palmitate effective and safe in patients with chronic Achilles tendinopathy compared to a placebo?

Study will be conducted in the Institute of Sports Medicine, Colombo 07. The eligible trial participant will be randomized into 1:1 ratio. Participants will be given 25000 IU of oral retinyl Palmitate (Vitamin A) or Placebo once daily for 12 weeks.

All participants will receive a standardized rehabilitation programme for Achilles tendinopathy. The IMP will be provided in 2.5ml dose in a pre-filled syringe. It is recommended that the liquid is taken with a meal or shortly afterwards. Study treatment will consist of 25,000IU which is one 2.5ml syringe dose daily.

Patients randomized to receive placebo will receive a 2.5ml syringe containing placebo. It will be orange in colour, smell and taste the same as the 2.5ml Retinyl Palmitate syringes. The placebo is manufactured similarly to the drug product but does not contain the drug substance. The difference in content is accounted for through the inclusion of additional Coconut Medium Chain Triglyceride (MCT) excipient. Drug dispensing will be as follows: • 1 box dispensed at Visit 2 (Day 1 of drug administration) • 2 boxes dispensed at Visit 3 (Day 28 of drug administration +/- 7 days)

a. Both male and female >=18 years b. Participating in competitive sport c. Confirmed clinical and /or imaging-based (MRI or Grey-scale ultrasound) diagnosis of chronic mid-portion Achilles tendinopathy d. Unable to regularly participate in their sport due to Achilles tendinopathy for the past minimum 3 months but no longer than 6 months

a. Previous Achilles tendon rupture on the affected side b. Previous Achilles tendon surgery on the affected side c. History of traumatic tears d. Unable or unwilling to adhere to standardised rehabilitation programme e. Previous history of arrythmias f. History of myocardial infarction or unstable angina within the past 12 months g. History of retinopathy h. Participant is already taking Vitamin A supplementation or other retinoid derivatives i. Participant is taking tetracyclines j. Known hereditary thrombophilia (Factor V Leiden, Protein C/ S deficiency, anti-phospholipid or anti-cardiolipin antibodies) k. Use of Vitamin K antagonist (such as Warfarin) l. Hepatic impairment (AST or ALT > 3 x upper limit of normal) m. Renal impairment (eGFR <10ml/ minute) n. History of moderate or severe hypercalcaemia (total albumin-corrected calcium > 3.0mmol/l) o. Active cancer (or recent cancer diagnosis within 6 months of screening) p. History of allergy or intolerance to retinoids q. Previous history of difficult to manage psychiatric disorders or history of suicidal ideation r. Pregnant or breast-feeding (or not willing to use an approved contraceptive method during treatment and for at least 1-month post treatment) s. Current enrolment in another interventional clinical trial t. Unable to tolerate oral medications u. Gastrointestinal problems that may affect oral drug absorption such as fat malabsorption v. Pancreatic disease w. Not able to consume fish oils/ gelatine-containing substances due to religious, cultural, health or other personal reasons