Assessing Bone Fracture Healing Effect of Almonds

NCT07153302 | Recruiting

• 2 other identifiers: 5822348053557
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.To compare the incidence of adverse events between almonds and vitamin D3 treatments up to 13 weeks follow-up.
3. 3.To compare the almonds and vitamin D3 treatment cost.
4. 4.To compare within group blood vitamin D levels (ng/mL) at baseline and post-treatment follow-ups.
5. 5.Regulatory and Ethical approvals.
6. 6.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.
7. 7.Written informed consent administration.
8. 8.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).
9. 9.Patients are followed at 4 weeks and 13 weeks follow-ups after treatment.
10. 10.Fracture site routine X-rays and RUST scores are assessed by treating surgeon/investigator(s) at follow-ups for bone fracture healing.
11. 11.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.
12. 12.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.
13. 13.Patients can withdraw from the study at any time without losing any of his/her patient rights.
14. 14.Study close-out process will be of one to two-month duration.

Conditions

Femur Shaft Fracture; Tibia Fractures; Vitamin D; Sweet Almonds; Callus Index; Callus Bridging

Keywords

callus bridging; callus index; femur shaft fracture; tibia shaft fracture; Prunus dulcis (almonds); vitamin D3

Outcome Measures

Primary Outcomes (3)

• Callus index

  Assessing mean difference in femur and tibia shaft fracture bone callus formation by measuring callus index (millimetre diameter) on x-ray (AP and ML/Lateral views) at follow-ups post-treatment. Callus index is defined as the ratio of the maximum callus diameter to bone diameter at the same level as the callus. Callus index determined for anteroposterior (AP) and mediolateral (ML) radiographs.

  comparable callus formation at 4 and 13 weeks post-treatment.

• Callus bridging

  Callus bridging on x-ray (AP and ML/Lateral views) at follow-ups post-treatment, the fracture heals by a periosteal bony callus at the periphery of the fracture and fibrocartilaginous bridging callus between bone ends. Radiographic union scale in tibial fractures (RUST) score standardize the radiographic assessment of tibial fractures by assessing cortical bridging and obliteration of fracture line. A RUST score of 1 (cortex with no callus and a visible fracture line), 2 (a bridging callus and a visible fracture line); and 3 (a callus and no visible fracture line). Low RUST score (4 or 5) indicates no or poor fracture healing. High score (11 or 12) indicates definite fracture healing.

  Comparable callus bridging at 4 and 13 weeks post-treatment,

• Investigational product safety

  Assessment of patient safety of all three treatment arms by serious adverse event (SAE)/adverse event (AE) incidence. Any untoward medical occurrence in a patient administered a medicinal product is called an AE. If any dose results in death, disability/incapacity, inpatient/prolonged hospitalization, and is life-threatening is called an SAE.

  Fifty percent fewer side effects after almonds than vitamin D3 treatments. SAE within 24 hours unexpected AE 15 days of knowing the event, SAE report submission within 5 days and unexpected AE in 15 days.

Secondary Outcomes (2)

• Blood Vitamin D level

  Blood vitamin D3 levels comparable after 28 days of almonds and 8 weeks after routine vitamin D3 treatments with one week washout time.

• Cost

  Almonds cost 28 days of treatment and vitamin D cost 8 weeks of treatment.

Study Arms (3)

Arm A

OTHER

Cross-over treatment Group 1 (N=14): Arm A (n=7) = 5±0.5 grams/day of whole almonds for 4 weeks, followed by 7 days washout period and initiating cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks.

Other: Prunus dulcis (sweet almonds)

Arm B

OTHER

Cross-over treatment Group 1 (N=14): Arm B (n=7) = Oral vitamin D3 200,000 units/week for 8 weeks, followed by 7 days washout period and initiating cross-over treatment by 5±0.5 grams/day of whole almonds for 4 weeks 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 initiating cross-over treatment by 5±0.5 grams/day of whole almonds for 4 weeks.

Other: Prunus dulcis (sweet almonds)

Arm C

OTHER

Cross-over treatment Group 2 (N=122): Arm C (n=61) = Oral vitamin D3 200,000 units/week together with 5±0.5 grams/day whole almonds for 4 weeks, followed by 7 days washout period and initiating cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks.

Other: Prunus dulcis (sweet almonds)

Interventions

Prunus dulcis (sweet almonds) OTHER

Almonds are functional food items that contain bone essential micronutrients.

Also known as: sweet almonds

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients of 18 to 55 years of age of any gender.
• Agree and able to voluntary participate.
• Patients with trauma associated femur fracture and tibia shaft fracture arriving at hospital for treatment.

You may not qualify if:

• Mentally retarded or patients with severe psychiatric illness.
• Patients are already on bone-strengthening drugs (bisphosphonates, vitamin D, strontium ranelate, teriparatide, etc.).
• Patients who require bone-strengthening drugs for osteoporosis or for any urgent need.
• Severe cardiovascular, hepatic, or renal disease.
• Known allergy or toxicity to Prunus dulcis (almonds) and/or vitamin D supplements.

Sponsors & Collaborators

• Aga Khan University Hospital, Pakistan: lead
• University of Karachi: collaborator
• PharmEvo Pvt Ltd: collaborator

Study Sites (1)

The Aga Khan University

Karachi, 74800, Pakistan

RECRUITING

Related Publications (13)

• Barreca D, Nabavi SM, Sureda A, Rasekhian M, Raciti R, Silva AS, Annunziata G, Arnone A, Tenore GC, Suntar I, Mandalari G. Almonds (Prunus Dulcis Mill. D. A. Webb): A Source of Nutrients and Health-Promoting Compounds. Nutrients. 2020 Mar 1;12(3):672. doi: 10.3390/nu12030672.

  PMID: 32121549 BACKGROUND

• Leow JM, Clement ND, Tawonsawatruk T, Simpson CJ, Simpson AH. The radiographic union scale in tibial (RUST) fractures: Reliability of the outcome measure at an independent centre. Bone Joint Res. 2016 Apr;5(4):116-21. doi: 10.1302/2046-3758.54.2000628.

  PMID: 27073210 BACKGROUND

• Whelan DB, Bhandari M, Stephen D, Kreder H, McKee MD, Zdero R, Schemitsch EH. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma. 2010 Mar;68(3):629-32. doi: 10.1097/TA.0b013e3181a7c16d.

  PMID: 19996801 BACKGROUND

• Eastaugh-Waring SJ, Joslin CC, Hardy JR, Cunningham JL. Quantification of fracture healing from radiographs using the maximum callus index. Clin Orthop Relat Res. 2009 Aug;467(8):1986-91. doi: 10.1007/s11999-009-0775-0. Epub 2009 Mar 13.

  PMID: 19283438 BACKGROUND

• Anaraki N, Beyraghi AH, Raisi A, Davoodi F, Farjanikish G, Sadegh AB. The effect of aqueous extract of Prunus dulcis on tibial bone healing in the rabbit. J Orthop Surg Res. 2021 Jun 7;16(1):362. doi: 10.1186/s13018-021-02498-z.

  PMID: 34098995 BACKGROUND

• Platt ID, Josse AR, Kendall CW, Jenkins DJ, El-Sohemy A. Postprandial effects of almond consumption on human osteoclast precursors--an ex vivo study. Metabolism. 2011 Jul;60(7):923-9. doi: 10.1016/j.metabol.2010.08.012. Epub 2010 Oct 13.

  PMID: 20947104 BACKGROUND

• Jamshed H, Arslan J, Sultan FT, Siddiqi HS, Qasim M, Hassan Gilani AU. Almond protects the liver in coronary artery disease: A randomized controlled clinical trial. J Pak Med Assoc. 2021 Mar;71(3):791-795. doi: 10.47391/JPMA.198.

  PMID: 34057922 BACKGROUND

• Jalali-Khanabadi BA, Mozaffari-Khosravi H, Parsaeyan N. Effects of almond dietary supplementation on coronary heart disease lipid risk factors and serum lipid oxidation parameters in men with mild hyperlipidemia. J Altern Complement Med. 2010 Dec;16(12):1279-83. doi: 10.1089/acm.2009.0693. Epub 2010 Nov 29.

  PMID: 21114415 BACKGROUND

• Zofkova I, Nemcikova P, Matucha P. Trace elements and bone health. Clin Chem Lab Med. 2013 Aug;51(8):1555-61. doi: 10.1515/cclm-2012-0868.

  PMID: 23509220 BACKGROUND

• Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients. 2021 Jan 26;13(2):368. doi: 10.3390/nu13020368.

  PMID: 33530332 BACKGROUND

• Fischer V, Haffner-Luntzer M, Amling M, Ignatius A. Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover. Eur Cell Mater. 2018 Jun 22;35:365-385. doi: 10.22203/eCM.v035a25.

  PMID: 29931664 BACKGROUND

• Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int. 2004 Sep;75(3):183-8. doi: 10.1007/s00223-004-0167-0.

  PMID: 15386160 BACKGROUND

• Brun-Buisson C. [Treatment of antibiotic-resistant bacteria at the intensive care unit: a therapy dilemma]. Int J Clin Pract Suppl. 2000 Jan;(109):4-5. No abstract available. Italian.

  PMID: 10765553 BACKGROUND

Study Officials

• Zehra A Muhammad, M.B.B.S., M.S. Research

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zehra A Muhammad, M.B.B.S., M.S. Research

CONTACT

+92 21 54864746; zehra.abdul@aku.edu

Tashfeen Ahmad, F.C.P.S., Ph.D.

CONTACT

+92 21 34864742; tashfeen.ahmad@aku.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Instructor

Model Details: Patients (N=136) are divided into two groups. Group 1 (vitamin D insufficiency, blood vitamin D level 21-29 ng/mL) and Group 2 (vitamin D deficiency, blood vitamin D level ≤20 ng/mL). Within two weeks of screening, patients are randomly allocated into a total of three arms. Note: If blood vitamin D level exceeds 50 ng/mL, the vitamin D administration will be discontinued by the trial team and treating surgeon will decide to continue it or not.

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 3, 2025
• Study Start: August 20, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After study close-out and on request.
• Access Criteria: At the time of publication (deidentified individual patient data and analysis plan) and on request after study close-out (Study protocol, clinical study report).

Locations

PA (1)