Evaluation of Hydroxymethylbutyrate Supplementation in Lung Transplant Candidates Receiving Pulmonary Rehabilitation

NCT07660991 | Completed

• 1 other identifier: OkanU-MO-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. It is important to optimize the nutritional status of patients during the waiting period before transplantation, to positively improve their vital functions such as exercise capacity, to get up as soon as possible after transplantation, to shorten the hospitalization process and to support survival. Pulmonary rehabilitation (PR) aims to prevent further progression of respiratory disease and improve the physical and mental health of patients, as well as helping patients to adopt healthy behavior habits. PR before transplantation helps individuals maintain or optimize their functional status before surgery. PR before transplantation helps individuals maintain or optimize their functional status before surgery. Beta-hydroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. Several studies have shown HMB supplements to be beneficial, either alone or in combination with other amino acids and exercise training, for maintaining and restoring lean body mass, muscle strength and function in older adults. HMB provides a decrease in muscle protein breakdown along with an increase in muscle protein synthesis. In addition, it stimulates muscle protein synthesis by activating the mechanical target of the mammals are the target of rapamycin (mTOR) system and growth hormone/insulin-like growth hormone. Given the very low amounts of HMB and the low conversion rate of leucine to HMB (5-10%), the optimal dose requirement of HMB cannot be met with a standard diet. Therefore, oral supplementation of HMB is seen as an alternative to alleviate adult metabolic diseases, muscle wasting and functional loss. In lung transplant candidates, it is important to optimize nutrition and health conditions during the listing period, to get up as soon as possible after transplantation, to shorten the hospitalization process and to support survival. The study aimed to investigate the positive/negative effects of pulmonary rehabilitation and HMB supplementation, which supports muscle mass and protein production, on patients compared to pulmonary rehabilitation alone in lung transplant candidates.

Conditions

Lung Transplantation; Pulmoner Rehabilitation; Lun Transplant Candidates

Keywords

lung transplantation; pulmonary rehabilitation; lung transplant candidates; hydroxymethylbutyrate

Outcome Measures

Primary Outcomes (10)

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' biochemical measurements fasting glucose was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. Fasting blood sugar is usually measured after 8-10 hours of fasting, and the normal range is 70-99 mg/dL.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participiants' 6-minute walk test was evaluated at the begining of the study and at the end of the 8-week study. The 6-minute walk test was performed by a physiotherapist from the lung transplant team. The normal distance for a 6-minute walking test is between 400-700m.

  From the registration stage to the end of the 8-week follow-up period.

• Comporasion of lung transplant candidates who received pulmonary rehabilitation, dietary therapy abd hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' respiratory function tests (FEV1, FVC AND FEV1/FVC) was evaluated at the begining of the study and at the end of the 8-week study. A pulmonary function test was performed by a nurse working at Koşuyolu High Specialization Training and Research Hospital. FEV1 and FVC values of 80% or higher are considered normal. The FEV1/FVC ratio is normally between 70% and 80%.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' body composition (weight (kilograms), height (meters), BMI (kg/m2)) was assessed at the beginning of the study and at the end of the 8-week study using a BC-420MA body analyzer and measuring tape. BMI is by dividing weight (kilograms) by the square of height (meters). Individuals with a BMI between 25.0 and 29.9kg/m2 were accepted.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' short form -36 (SF-36) quality of life scale was evaluated at the beginning of the study and at the end of the 8-week study. SF-36 quality of life scale scores were evaluated and compared at the beginning and end of the study. Higher scores on the SF-36 scale indicate a better quality of life. The score ranges from a minimum of zero to a maximum of one hundred points.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' biochemical measurements (total protein, prealbumin, albumin) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal range for total serum protein is 6.0 to 8.3 g/dl. The normal range for prealbumin is 15-36 mg/dl. The normal range for serum albumin is 34-54 mg/dl.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy

  Participants' biochemical measurements (urea, creatinine) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal range for serum urea is 10-50 mg/dl. The normal serum creatinine range is 0.5-1.1 mg/dl for women and 0.6-1.2 mg/dl for men.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' biochemical measurements (total cholesterol, triglyceride) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal value for serum total cholesterol should be below 200 mg/dl. The normal value for serum total triglycerides should be below 150 mg/dl.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' body composition (lean body mass (FFM), body fat percentage, body muscle mass, body fat mass) was assessed at the beginning of the study and at the end of the 8-week study using a BC-420MA body analyzer and measuring tape. The normal FFM value should be 75-85% for women and 80-90% for men. The normal range for body fat percentage is 25-31% for women and 18-24% for men.

  From the registration stage to the end of the 8-week follow-up period.

• Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.

  Participants' body composition (waistcircumference, hip circumference, waist-to-hip ratio, upper mid-arm circumference, calf circumference) was assessed at the beginning of the study and at the end of the 8-week study using a measuring tape. Waist circumference should be below 80cm for women and 94cm for men. A waist-to-hip ratio of 0.85 or less is considered normal for women, and 0.90 or less for men. An upper mid-arm circumference of 22cm or more is considered normal for women, and 23cm or more for men. A calf circumference of 31-36 cm is considered normal for women, and 35-38 cm for men.

  From the registration stage to the end of the 8-week follow-up period.

Study Arms (1)

hmb arm

EXPERIMENTAL

Participants of half will be given hydroxymethylbutyrate for 2 months. all participants will take pulmonary rehabilitation.

Dietary Supplement: HMB

Interventions

HMB DIETARY_SUPPLEMENT

Participants of half will be given hydroxymethylbutyrate for 2 months.

hmb arm

Eligibility Criteria

• Age: 40 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who volunteer to participate in the study,
• years of age
• BMI: 25.0kg/m² - 29.9kg/m²
• Lung transplant candidates,
• Suitable for pulmonary rehabilitation,
• Suitable after consultation with psychiatrists, cardiologist, and orthopedists,
• Hemodynamically stable,
• Patients who have the ability to receive and follow instructions will be included.

You may not qualify if:

• Participants were excluded from the study if they were: • Not a lung transplant candidate
• Not Turkish-speaking
• Malnourished
• Had a chronic disease such as diabetes, hypertension, cancer, metabolic syndrome, chronic renal failure, etc.
• Were deemed ineligible after psychiatric, cardiological, or orthopedic consultations
• Pregnant or breastfeeding
• Used any oral nutritional supplement containing HMB before the study
• Ineligible for pulmonary rehabilitation for any reason
• Participants could withdraw from the study at any time during the study.

Sponsors & Collaborators

• Okan University: lead

Study Sites (1)

Koşuyolu Yüksek Ihtisas Eğitim Ve Araştırma Hastanesi

Istanbul, Kartal, 34865, Turkey (Türkiye)

Location

Related Publications (24)

• Duan Y, Li F, Li Y, Tang Y, Kong X, Feng Z, Anthony TG, Watford M, Hou Y, Wu G, Yin Y. The role of leucine and its metabolites in protein and energy metabolism. Amino Acids. 2016 Jan;48(1):41-51. doi: 10.1007/s00726-015-2067-1. Epub 2015 Aug 9.

  PMID: 26255285 BACKGROUND

• Ding Q, Chen W, Chen C, Zhu YM, Yang WW, Ding JR. Evaluation of nutritional status in lung transplant recipients and its correlation with post-transplant short-term prognosis: a retrospective study. Ann Transl Med. 2022 Jul;10(14):793. doi: 10.21037/atm-22-3125.

  PMID: 35965836 BACKGROUND

• Courel-Ibanez J, Vetrovsky T, Dadova K, Pallares JG, Steffl M. Health Benefits of beta-Hydroxy-beta-Methylbutyrate (HMB) Supplementation in Addition to Physical Exercise in Older Adults: A Systematic Review with Meta-Analysis. Nutrients. 2019 Sep 3;11(9):2082. doi: 10.3390/nu11092082.

  PMID: 31484462 BACKGROUND

• Cornelison SD, Pascual RM. Pulmonary Rehabilitation in the Management of Chronic Lung Disease. Med Clin North Am. 2019 May;103(3):577-584. doi: 10.1016/j.mcna.2018.12.015.

  PMID: 30955523 BACKGROUND

• Chicago Universitesi Pritzker Tip Fakultesi, Gogus Hastaliklari ve Yogun Bakim Bilim Dali, Chicago, ABD, & Bag, R. (2020). General Indications and Patient Selection in Lung Transplantation. Güncel Göğüs Hastalıkları Serisi, 8(1), 20-31. https://doi.org/10.5152/gghs.2020.002

  BACKGROUND

• Arjuna A, Olson MT, Walia R. Current trends in candidate selection, contraindications, and indications for lung transplantation. J Thorac Dis. 2021 Nov;13(11):6514-6527. doi: 10.21037/jtd-2021-09.

  PMID: 34992831 BACKGROUND

• Wouters EFM, Wouters BBREF, Augustin IML, Houben-Wilke S, Vanfleteren LEGW, Franssen FME. Personalised pulmonary rehabilitation in COPD. Eur Respir Rev. 2018 Mar 28;27(147):170125. doi: 10.1183/16000617.0125-2017. Print 2018 Mar 31.

  PMID: 29592864 BACKGROUND

• Tuncay, F. (2021). Pulmoner rehabilitasyon. Journal of Physical Medicine and Rehabilitation Sciences, 24(2):169-179.

  BACKGROUND

• Troosters T, Janssens W, Demeyer H, Rabinovich RA. Pulmonary rehabilitation and physical interventions. Eur Respir Rev. 2023 Jun 7;32(168):220222. doi: 10.1183/16000617.0222-2022. Print 2023 Jun 30.

  PMID: 37286219 BACKGROUND

• Suzuki H, Yoshino I. A narrative review on the management of patients awaiting lung transplantation in Japan. J Thorac Dis. 2023 Oct 31;15(10):5856-5862. doi: 10.21037/jtd-22-1690. Epub 2023 Oct 20.

  PMID: 37969266 BACKGROUND

• Prado CM, Orsso CE, Pereira SL, Atherton PJ, Deutz NEP. Effects of beta-hydroxy beta-methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1623-1641. doi: 10.1002/jcsm.12952. Epub 2022 Mar 17.

  PMID: 35301826 BACKGROUND

• Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J. Interpretative strategies for lung function tests. Eur Respir J. 2005 Nov;26(5):948-68. doi: 10.1183/09031936.05.00035205. No abstract available.

  PMID: 16264058 BACKGROUND

• National Institutes of Health (NIH), National Cancer Institute (NCI). Dietary Assessment Primer. 24-hour Dietary Recall (24HR) At a Glance. Bethesda, MD: National Cancer Institute (2014).

  BACKGROUND

• Molfino A, Gioia G, Rossi Fanelli F, Muscaritoli M. Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials. Amino Acids. 2013 Dec;45(6):1273-92. doi: 10.1007/s00726-013-1592-z. Epub 2013 Sep 22.

  PMID: 24057808 BACKGROUND

• Makhdami N, Farooqi M, Thom-Fernandes C, Raghavan NG. Pulmonary rehabilitation in interstitial lung diseases. Curr Opin Pulm Med. 2020 Sep;26(5):470-476. doi: 10.1097/MCP.0000000000000700.

  PMID: 32769674 BACKGROUND

• Langer D. Rehabilitation in Patients before and after Lung Transplantation. Respiration. 2015;89(5):353-62. doi: 10.1159/000430451. Epub 2015 Apr 30.

  PMID: 25924770 BACKGROUND

• Landi F, Calvani R, Picca A, Marzetti E. Beta-hydroxy-beta-methylbutyrate and sarcopenia: from biological plausibility to clinical evidence. Curr Opin Clin Nutr Metab Care. 2019 Jan;22(1):37-43. doi: 10.1097/MCO.0000000000000524.

  PMID: 30489401 BACKGROUND

• Koçyiğit, H., Aydemir, Ö., Fişek, G., Ölmez, N., Memiş, A. (1999). Kısa form-36'nın Türkçe verisyonunun güvenilirliği ve geçerliliği. İlaç ve Tedavi Dergisi, 12(2), 102-106.

  BACKGROUND

• Hollander FM, van Pierre DD, de Roos NM, van de Graaf EA, Iestra JA. Effects of nutritional status and dietetic interventions on survival in Cystic Fibrosis patients before and after lung transplantation. J Cyst Fibros. 2014 Mar;13(2):212-8. doi: 10.1016/j.jcf.2013.08.009. Epub 2013 Sep 13.

  PMID: 24041590 BACKGROUND

• Hoffman M, Chaves G, Ribeiro-Samora GA, Britto RR, Parreira VF. Effects of pulmonary rehabilitation in lung transplant candidates: a systematic review. BMJ Open. 2017 Feb 3;7(2):e013445. doi: 10.1136/bmjopen-2016-013445.

  PMID: 28159852 BACKGROUND

• He X, Duan Y, Yao K, Li F, Hou Y, Wu G, Yin Y. beta-Hydroxy-beta-methylbutyrate, mitochondrial biogenesis, and skeletal muscle health. Amino Acids. 2016 Mar;48(3):653-664. doi: 10.1007/s00726-015-2126-7. Epub 2015 Nov 14.

  PMID: 26573541 BACKGROUND

• Afonso Junior JE, Werebe Ede C, Carraro RM, Teixeira RH, Fernandes LM, Abdalla LG, Samano MN, Pego-Fernandes PM. Lung transplantation. Einstein (Sao Paulo). 2015 Apr-Jun;13(2):297-304. doi: 10.1590/S1679-45082015RW3156.

  PMID: 26154550 BACKGROUND

• Perez AA, Shah RJ. Critical Care of the Lung Transplant Patient. Clin Chest Med. 2022 Sep;43(3):457-470. doi: 10.1016/j.ccm.2022.04.007.

  PMID: 36116814 BACKGROUND

• Young KA, Dilling DF. The Future of Lung Transplantation. Chest. 2019 Mar;155(3):465-473. doi: 10.1016/j.chest.2018.08.1036. Epub 2018 Aug 29.

  PMID: 30171860 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: registered dietitian

Model Details: The study was designed as a randomized controlled trial. The study consisted of control and experimental groups, including participants receiving Diet+PR and Diet+PR+HMB. Participants' inclusion groups will be determined by a draw. All participants who met the study inclusion criteria will provide informed consent and will be administered a sociodemographic questionnaire, a 24-hour food intake record, the NRS2002 form, the sf-36 quality of life scale, anthropometric measurements, biochemical measurements, the 6MWT, the PFT, and a handgrip strength test. Each participating patient will participate in a PR program with a physical therapist, consisting of 45-minute sessions, three days a week, for eight weeks. Each patient will be provided with a diet plan and training tailored to their needs.

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: June 22, 2026
• Study Start: June 10, 2025
• Primary Completion: September 30, 2025
• Study Completion: January 31, 2026
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)