Evaluation of Hydroxymethylbutyrate Supplementation in Lung Transplant Candidates Receiving Pulmonary Rehabilitation

Pulmoner Rehabilitasyon Alan akciğer Nakil adaylarında hidroksimetilbütirat Takviyesinin değerlendirilmesi

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.

Study Overview

• Status: Completed
• Conditions: Lung Transplantation; Pulmoner Rehabilitation; Lun Transplant Candidates
• Intervention / Treatment: Dietary supplement: HMB

Detailed Description

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. Primary indications for lung transplantation in the world are; 34% chronic obstructive pulmonary disease (COPD), 24% idiopathic pulmonary fibrosis (IPF), 17% cystic fibrosis (CF), 6% alpha-1-antitrypsin deficiency, 3% idiopathic pulmonary arterial hypertension (IPAH), 4% pulmonary fibrous (non-IPF), 3% bronchiectasis, 2.6% re transplantation and 2.5% of them are classified as sarcoidosis. Absolute contraindications for lung transplantation are; active malignancy, coronary artery disease without revascularization ability, significant extrapulmonary organ dysfunction, active tobacco or bad substance use, the presence of extremely serious active infections such as tuberculosis, morbid obesity and lack of psychosocial support. Absolute contraindications for lung transplantation are; active malignancy, coronary artery disease without revascularization ability, significant extrapulmonary organ dysfunction, active tobacco or bad substance use, the presence of extremely serious active infections such as tuberculosis, morbid obesity and lack of psychosocial support. Some relative contraindications are critical illness, mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) support, each transplant center has a different attitude. The upper age limit for lung transplantation varies according to each center, but is generally accepted as between 70 and 75 years of age. Beta-hydroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine.roxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. HMB is found in very small amounts in some foods such as avocados, citrus fruits, caulidroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. HMB is found in very small amounts in some foods such as avocados, citrus fruits, cauliflower and catfish. Leucine has a specific role in the regulation and control of protein synthesis in muscle cells. About 5% of leucine in the body is converted into HMB. Many studies have shown that HMB supplements alone or in combination with other amino acids and in combination with exercise training are beneficial for maintaining and restoring lean body mass, muscle strength and function in older adults. Many studies have shown that HMB supplements alone or in combination with other amino acids and in combination with exercise training are beneficial for maintaining and restoring lean body mass, muscle strength and function in older adults. Leucine is the most effective branched chain amino acid in important cellular processes such as protein synthesis and energy metabolism. The first step in leucine metabolism in the body is the reversible transamination that occurs in skeletal muscles to form α-ketoisocaproate with simultaneous production of glutarate from α-ketoglutarate. The first step in leucine metabolism in the body is the reversible transamination that occurs in skeletal muscles to form α-ketoisocaproate with simultaneous production of glutarate from α-ketoglutarate. The second stage is the irreversible oxidative decarboxylation of α-ketoisocaproate by branched-chain α-keto acid dehydrogenase (BCKD) and α-ketoisocaproate dehydrogenase (KICD) enzymes. In liver mitochondria, 90% of the α-ketoisocaproate produced causes the formation of acetoacetate and acetyl CoA, while in liver cytosol, the remaining 5-10% α-ketoisocaproate is oxidized to HMB by the enzyme KICD. Liver mitochondria, 90% of the α-ketoisocaproate produced causes the formation of acetoacetate and acetyl CoA, while in liver cytosol, the remaining 5-10% α-ketoisocaproate is oxidized to HMB by the enzyme KICD. 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 rapamyc November (mTOR) system and growth hormone/insulin-like growth hormone. HMB has also been shown to be associated with a decrease in muscle proteolysis by inhibiting the ubiquitin-proteasome and autophagy-lysosome systems. Given the very low amounts of HMB present in foods and the low conversion rate of leucine to HMB (5-10%), optimal HMB dose requirements cannot be met with a standard diet. Therefore, oral HMB supplementation is considered an alternative to alleviate adult metabolic diseases, muscle wasting, and functional loss. Pulmonary rehabilitation (PR) aims to prevent further progression of respiratory disease and improve patients' physical and mental health, while also encouraging patients to adopt healthy behavioral habits. The European Respiratory Society and the American Thoracic Society define PR as "patient-specific treatments, including but not limited to exercise training and behavior modification, designed to improve the physical and psychological well-being of individuals with chronic respiratory diseases and to promote long-term health-promoting behaviors." PR, which includes exercise training, is a powerful intervention designed to improve exercise tolerance, skeletal and respiratory muscle function, movement efficiency, symptoms of dyspnea and fatigue, and health-related quality of life. PR aims to stabilize or reverse the pathophysiological and psychopathological symptoms of the disease and strives to restore the patient to the highest possible functional capacity. The optimal exercise type, duration, intensity, and frequency for PR have not yet been determined. A minimum of eight weeks is generally recommended for PR programs to provide lasting benefits to the patient. Exercise sessions are generally scheduled 3-5 times a week, each session lasting 20-45 minutes. It is suggested that the improvement mechanism of exercise training is related to increasing aerobic capacity and peripheral muscle performance in patients. Exercise intolerance and decreased quality of life often persist after transplantation. Physiological changes associated with severe chronic lung disease, extremity muscle dysfunction, inactivity/deconditioning, and nutritional deficiencies can affect exercise capacity and physical functioning in lung transplant candidates. Prolonged post-transplant hospital and intensive care unit stays, prolonged immobilization, immunosuppressant medications, and organ rejection can all impact lung recipients' recovery in terms of exercise tolerance and quality of life. Decreases in muscle mass and quadriceps strength are frequently observed in the pre-transplant period and have been reported to persist for up to 3 years post-transplant. Pre-transplant PR helps individuals maintain or optimize their pre-operative functional status. The nutritional status of patients on the waiting list is associated with post-transplant survival. Studies have identified obesity, low body mass index, and low serum albumin concentration as significant risk factors for increased mortality after lung transplantation. Nutritional status in lung transplant candidates is associated with post-transplant survival. Obesity, as well as pre-transplant malnutrition, is considered a contraindication and appears to increase the risk of post-transplant mortality independently of other risk factors. Lean body mass (FFM) is an important indicator of nutritional status. It is associated with muscle mass, muscle function, lung function, and quality of life. A decrease in FFM is significantly associated with increased mortality while waiting for transplantation and prolonged intensive care unit stay after transplantation. Body mass index (BMI) is a parameter used to assess nutritional status, calculated by dividing body mass by the square of height in meters. The resulting BMI is evaluated according to the World Health Organization (WHO) classification. A BMI above 30 kg/m² or below 18.5 kg/m² has been shown to increase post-transplant mortality and primary graft dysfunction. Furthermore, low albumin levels have frequently been associated with adverse post-transplant outcomes. In patients with end-stage lung disease, significant loss of lung function, respiratory failure, recurrent infections, decreased appetite caused by hypoxia and depression, and gastrointestinal dysfunction all contribute to inadequate energy intake and, consequently, malnutrition and even cachexia. The various complications associated with malnutrition lead to increased frequency and duration of hospitalization and shortened survival after transplantation. Therefore, it is crucial to assess the nutritional status of lung transplant candidates before transplantation, identify any risks of malnutrition in a timely manner, and provide an individualized nutrition program tailored to each patient. Optimizing nutrition and health status in lung transplant candidates during the listing period is crucial for achieving recovery as quickly as possible after transplantation, shortening hospital stays, and promoting survival. The study aimed to investigate the positive/negative effects of pulmonary rehabilitation and HMB supplementation, which supports muscle mass and protein synthesis, compared to pulmonary rehabilitation alone in lung transplant candidates.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Kartal
    • Istanbul, Kartal, Turkey (Türkiye), 34865
      • Koşuyolu Yüksek Ihtisas Eğitim Ve Araştırma Hastanesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who volunteer to participate in the study,

  • 40-50 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.

Exclusion Criteria:

• 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
  • Were found to be non-compliant with dietary/supplement interventions during follow-up after inclusion in the study.
  • Participants could withdraw from the study at any time during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hmb arm; Participants of half will be given hydroxymethylbutyrate for 2 months. all participants will take pulmonary rehabilitation.	Dietary supplement: HMB; Participants of half will be given hydroxymethylbutyrate for 2 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Okan University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• 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.
• 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.
• Tuncay, F. (2021). Pulmoner rehabilitasyon. Journal of Physical Medicine and Rehabilitation Sciences, 24(2):169-179.
• 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.
• 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.
• 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).
• 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.
• Langer D. Rehabilitation in Patients before and after Lung Transplantation. Respiration. 2015;89(5):353-62. doi: 10.1159/000430451. Epub 2015 Apr 30.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2025
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): January 31, 2026

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: pulmonary rehabilitation; lung transplantation; hydroxymethylbutyrate; lung transplant candidates
• Other Study ID Numbers: OkanU-MO-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No