Assessing Bone Fracture Healing Effect of Prunus Dulcis (Almonds) - A Randomized Controlled Trial

Femur and tibia shaft fractures are common after trauma with a burden of 5% and 20% respectively. Clinicians recommend costly bone strengthening drugs/supplements while treating bone fractures. These drugs have side effects and are costly due to which patients skip these supplements. Routinely prescribed vitamin D have known toxicity. To overcome this problem, affordable and safe alternative treatment is needed. Sweet almonds contain essential bone nutrients that might have potential for maintaining bone strength. Human and animal studies have shown positive impact of almonds on bone health and fracture healing. Almonds are consumed in diet frequently but may occasionally cause toxicity, mainly if consumed at higher amount. Because of the high bone essential nutrients in almonds, the trial aimed to investigate the fracture healing effect and safety of almonds in femur and tibia shaft fractures. This might provide an alternate option for bone supplants while treating fractures.

Hypothesis: Compared to routine vitamin D3, almonds non-inferiorly improves fracture callus index and raise vitamin D3 level in blood in femur and tibia shaft fracture patients.

Primary Objectives:

1. To compare tibia and femur shaft fracture callus index and callus bridging on x-rays at 4 and 13 weeks herewith group 1 suffering vitamin D insufficiency (arm A versus arm B) and group 2 suffering vitamin D deficiency (arm B versus arm C) treated as cross-over with oral whole almonds and vitamin D3.
2. To compare the incidence of adverse events between almonds and vitamin D3 treatments up to 13 weeks follow-up.

Secondary Objectives:

1. To compare the almonds and vitamin D3 treatment cost.
2. To compare within group blood vitamin D levels (ng/mL) at baseline and post-treatment follow-ups.

Methods:

Study design: Single-center, open-labeled, crossover, non-inferiority randomized controlled trial.

Total 136 subjects are required with 14 subjects in group 1 and 122 in group 2.in 24-month duration.

Study procedures:

1. Regulatory and Ethical approvals.
2. Patient screening and eligibility assessment. Patients, of 18 to 55 years of age of any gender, with trauma associated femur and tibia shaft fractures who agree to voluntary participate are included and mentally retarded or patients with severe psychiatric illness, already on or require bone-strengthening drugs , having severe cardiovascular, hepatic, or renal disease, known allergy/toxicity to almonds and/or vitamin D supplements.
3. Written informed consent administration.
4. Randomization Patients (N=136) are divided into two groups. Group 1 (N=14, vitamin D insufficiency, blood vitamin D level 21-29 ng/mL) and Group 2 (N=122, vitamin D deficiency, blood vitamin D level ≤20 ng/mL).

I. Group 1 (N=14):

Arm A (n=7)=5 grams/day of almonds for 4 weeks, followed by 7 days washout period and cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks.

Arm B (n=7)=Oral vitamin D3 200,000 units/week for 8 weeks, followed by 7 days washout period and cross-over treatment by 5 grams/day of almonds for 4 weeks

II. Group 2 (N=122):

Arm B (n=61)=Oral vitamin D3 200,000 units/week for 8 weeks, followed by 7 days washout period and cross-over treatment by 5 grams/day of almonds for 4 weeks.

Arm C (n=61)=Oral vitamin D3 200,000 units/week together with 5 grams/day almonds for 4 weeks, followed by 7 days washout period and cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks. 5. Patients are followed at 4 weeks and 13 weeks follow-ups after treatment. 6. Fracture site routine X-rays and RUST scores are assessed by treating surgeon/investigator(s) at follow-ups for bone fracture healing. 7. Investigational product (IP) safety assessment and reporting as per ICH-GCP guidelines. Subjects experiencing any adverse event (AE)/serious adverse event (SAE) is provided optimum care at earliest. All relevant reporting bodies are notified within recommended timeline. 8. The almonds are regularly purchased from the Purchase Department of the Hospital, weighted, packaged and labelled, and stored at the secure dry hygienic place. The product is dispensed to the patient and a daily IP diary is provided for compliance. 9. Patients can withdraw from the study at any time without losing any of his/her patient rights. 10. Study close-out process will be of one to two-month duration.

Statistical analysis:

The SPSS version 19.0 will be used to analyze data. Quantitative variables will be expressed as mean±SD/median (IQR) and qualitative as frequencies (%). IP related AEs/SAEs will be assessed by incidence/stratification. Witin group and within arm comparisons for the radiological assessments and vitamin D3 level will be analyzed by ANOVA and GEE. Within arm tibia and femur fracture outcomes will be compared by independent t-test/Mann Whitney U test. The p-value <0.05 is considered significant. Multiple regression analysis for association of covariates and outcome will be used.