Effect of Vitamin D3 on Lung Function and Exercise Tolerance in D3 Deficient COPD Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Lung function (Spirometric variables) Forced Vital Capacity(FVC) will be changed
研究概览
简要总结
Background: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality throughout the world which is a preventable as well as treatable disease. It has some important extra pulmonary effects which may contribute to the magnitude of the severity of this disease. Standard therapeutic treatment alone does not optimize its remedy. Vitamin D3 has been found to improve the physical efficiency of patients with various morbid disorders, including respiratory ailments. Hypothesis:Vitamin D3 administration in stable patients with moderate COPD improves lung function variables along with exercise tolerance.
Objectives: To evaluate the effects of Vitamin D3 on lung functions and exercise tolerance in patients with stable moderate COPD. Methods: For this, a prospective interventional randomized double blinded study will be carried out on 46 vitamin D3 deficient (serum 25 dihidroxycholecalceferol less than 30 ng/ml), male, stable (diagnosed patient, who has not experienced any acute exacerbation , hospitalizations , urgent care visits, or changes in routine medication within 4 weeks prior to study), moderate (post bronchodilator FEV1/FVC<0.70 of predicted value and FEV1=50 to 79% of predicted value) COPD patients (age ≥40 years), who will be selected from the Out Patient Department (OPD) of the National Institute of Diseases of Chest and Hospital (NIDCH) and will be grouped as A (control) and B (study) groups, respectively. All the patients will be again designated as A0, A90 (without D3) and B0, B90 (with D3) for before and after 90 days of follow up. All the participants will be matched in terms of duration of COPD, history of smoking, occupation and socioeconomic status. Along with the standard pharmacological treatment of COPD, the patients of the 'Study group' will be prescribed for 80000 IU of oral vitamin D3 pre week for consecutive 3 months. Along with this, all patients both the groups will be advised to continue ad lib (according to their own choice) diet. At the very 1st day of the study, the lung functions will be assessed by measuring Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1), Forced expiratory ratio (FEV1/FVC%), Peak expiratory flow rate (PEFR) and Forced mid expiratory flow of FVC(FEF25-75%), with a portable digital spirometer. In addition, exercise tolerance will be assessed by change in 6 Minute Walk Distance (6MWD) in 6 Minute Walk Test (6MWT). Changes in peripheral capillary oxygen saturation (SpO2) by Pulse Oximeter and degree of dyspnoea by Modified Borg Scale (MBS) will also be measured both before and after 6MWT to evaluate their change in both the groups. All these variables will be measured again among same 46 patient after 90 days standard pharmacological treatment of COPD with D3 intervention (B group) and also without D3 intervention (A group). For statistical analysis, Chi-square test, independent sample 't' test between two groups, paired Student's 't' test within two specific measurements of different durations of each group ,will be done. In the interpretation of results, ≤0.05 level of probability (p) will be accepted as significant.
详细描述
- Introduction:
Chronic Obstructive Pulmonary Disease (COPD) is one of the major causes of chronic morbidity and mortality throughout the world . Many people suffer from the disease for years and die too early from its complications. COPD is the fourth leading cause of death in adults of United States and also projected to be the third by 2020 .Though it is a preventable and treatable disease, once developed the disease along with its comorbidities cannot be cured. But its progression and morbidity can be reduced.
The airflow obstruction in this disease is generally persistent as well as progressive .It has two clinical phases (stable phase and exacerbation phase), both of which are associated with inflammation .Independent risk factors for COPD are male gender, advanced age, low socioeconomic status, occupational exposure and cigarette smoking (both active and passive) ,reactivity of airways, occupational factors and air pollution .
Vitamin D is a steroid important in bone mineralization and calcium homeostasis. The prevalence of vitamin D deficiency has been increasing in the general population in recent decades. The majority of circulating 25-hydroxyvitamin D [25(OH)D] is derived from sun exposure with a limited dietary contribution. The increased prevalence of vitamin D deficiency is attributed to sun avoidance, indoor lifestyle, use of sunscreen, and decreased intake of vitamin D-containing foods .Because vitamin D is sequestered in adipose tissue, the increasing prevalence of obesity also increases the prevalence of vitamin D deficiency .
Recently, research has found that vitamin D may play a role in multiple chronic diseases such as cancer, autoimmune diseases, infections, and cardiovascular disorders . Vitamin D may also have a role in several diseases involving the respiratory system. Recently some researchers reported that a significant proportion of young COPD patients may have insufficient (20 to 29 ng/ml) serum 25-OHD . Moreover, higher serum vitamin D concentrations, assessed by [25(OH)D], have been associated with better lung function as measured by FEV1 in a large cross-sectional study of the U.S. population . Although the precise connection between vitamin D status and lung function is not clear at this point, it is postulated that vitamin D may improve lung function through its action on regulating inflammation ,inducing antimicrobial peptides , and/or its action on muscles .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Prospective interventional randomized double blinded study
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Socioeconomic status: Middle class
- •Stable patients of COPD with >1year duration
- •Vitamin D3 deficient :
- •Serum 25-hydroxycholecalciferol, [25(OH)D] level <30ng/ml (Vitamin D Council 2017)
排除标准
- •With acute exacerbation of any pulmonary diseases, as,
- •with acute exacerbation of any cardiac disease, like -
- •Uncontrolled systemic hypertension
- •Chronic liver disease
- •Malignancy
- •Use of drugs known to affect vitamin D metabolism within 1 month prior to With biochemical evidence of -
- •uncontrolled diabetes mellitus and
- •renal insufficiency
- •All the criteria mentioned above were scrutinized by taking history and clinical examination, except vitamin D3 deficiency, uncontrolled diabetes mellitus and renal insufficiency, which were diagnosed biochemically.
研究组 & 干预措施
A0
A0- On day 0,before intervention placebo,
- Microcrystalline Cellulose (303.8gm)
- Butylated Hydroxy Toluene (0.2mg)
- Magnesium Stearate (3mg)
- Gelatin Capsule Shell (1mg)
weekly,orally,for 90days
干预措施: Cholecalciferol (Drug)
A90
A90- On day 90,after intervention placebo,
- Microcrystalline Cellulose (303.8gm)
- Butylated Hydroxy Toluene (0.2mg)
- Magnesium Stearate (3mg)
- Gelatin Capsule Shell (1mg)
weekly,orally,for 90days
干预措施: Cholecalciferol (Drug)
B0
B0- On day 0,before intervention cholecalciferol,
- Cholecalciferol (40,000IU)
- Microcrystalline Cellulose (58.1 gm)
- Butylated Hydroxy Toluene ( 0.2mg)
- Magnesium Stearate (3mg)
- Gelatin Capsule Shell (1mg)
80.000IU/week,orally,for 90 days
干预措施: Cholecalciferol (Drug)
B90
B90- On day 90,after intervention cholecalciferol,
- Cholecalciferol (40,000IU)
- Microcrystalline Cellulose (58.1 gm)
- Butylated Hydroxy Toluene ( 0.2mg)
- Magnesium Stearate (3mg)
- Gelatin Capsule Shell (1mg)
80.000IU/week,orally,for 90 days
干预措施: Cholecalciferol (Drug)
结局指标
主要结局
Lung function (Spirometric variables) Forced Vital Capacity(FVC) will be changed
时间窗: After 90 days FVC will be measured again
Forced Vital Capacity It is the volume of air that can be expired as forcefully and rapidly as possible after maximal inspiration. In adult male it is about 4.6 liters. The FVC is commonly reduced in obstructive processes such as COPD.Increment of Forced Vital Capacity means improvement in outcome.
Lung function [ Lung function (Spirometric variables): Forced Expiratory Volume in 1st second(FEV1) will be changed
时间窗: After 90 days FEV1 will be measured again
Forced Expiratory Volume in 1st second When a person inspires maximally and exhales forcefully, then the volume, which is exhaled in 1st second is known as 'Forced Expiratory volume in 1st second'. It is normally 80% of forced vital capacity . Significance- This measurement is much more sensitive index of severity of the obstructive disease .In COPD ,FEV1 is reduced ,Increment of FEV1 indicates improvent in outcome
Lung function (Spirometric variables) Forced Expiratory Ratio [FEV1/FVC Ratio (%)] will be changed
时间窗: After 90 days FEV1/FVC Ratio will be measured again
Forced Expiratory Ratio It is the ratio of FEV1 to FVC expressed in percentage. FEV1/FVC ratio = FEV1/FVC×100. It is about 70% or higher. Forced Expiratory Ratio is less than 70% in COPD patients.Increment of Forced Expiratory Ratio indicates improvement in outcome
Lung function (Spirometric variables) Peak Expiratory Flow Rate [PEFR (L/min)] will be changed
时间窗: After 90 days PEFR will be measured again
Peak Expiratory Flow Rate It is the maximum expiratory rate, beyond which the flow cannot be increased even with greatly increased additional force. In adult it is about 400-700 Liter/second.
Lung function (Spirometric variables) Forced Expiratory Flow in the middle of FVC [FEF 25-75 (Liter/Second) ] will be changed
时间窗: After 90 days FEF 25-75 will be measured again
Forced Expiratory Flow in the middle of FVC Forced expiratory flow during the middle half of the FVC. Formerly it was called the maximal mid-expiratory flow (MMEF), expressed in liters/second Normal range in male : 1.5-4.5 Liter/second.Increment of Forced Expiratory Flow in the middle of FVC means improvement in outcome.
Lung function (Spirometric variables) Maximum expiratory Flow rate at 25%of the FVC (MEF 75) will be changed
时间窗: After 90 days MEF 75 will be measured again
Maximum expiratory Flow rate at 25%of the FVC (MEF 75) Maximum expiratory flow rate when 25% of the FVC remains in the lung to be exhaled and is equivalent to the FEF75 where 75% of the FVC has been exhaled. Expressed in liters/second. This is reduced in COPD. Increment in maximum expiratory flow at 25%of the FVC means improvement in outcome
Lung function (Spirometric variables) Maximum expiratory Flow at 50%of the FVC(MEF50) will be changed
时间窗: After 90 days MEF 50 will be measured again
Maximum expiratory Flow at 50%of the FVC(MEF50) Maximum expiratory flow rate when 50 % of the FVC remains in the lung to be exhaled and is equivalent to the FEF50 where 50% of the FVC has been exhaled. Expressed in liters/second. This is reduced in COPD. Increment in maximum expiratory flow at 50%of the FVC means improvement in outcome.
Lung function (Spirometric variables) Maximum expiratory Flow at 75%of the FVC (MEF25)]will be changed
时间窗: After 90 days MEF25 will be measured again
Maximum expiratory Flow at 75%of the FVC (MEF25) Maximum expiratory flow rate when 75% of the FVC remains in the lung to be exhaled and is equivalent to the FEF25 where 25% of the FVC has been exhaled. Expressed in liters/second.This is reduced in COPD.Increment in maximum expiratory flow at 75%of the FVC means improvement in outcome
Exercise Tolerance [Oxygenation variables] Peripheral Capillary Oxygen saturation[SpO2 (%) ] will be changed
时间窗: After 90 days SpO2 will be measured
Oxygenation variables Peripheral Capillary Oxygen saturation between 96% to 99% is normal.Peripheral Capillary Oxygen saturation between 96% to 99% means improved outcome
Exercise Tolerance variables Level of fatigue: Modified Borg Scale will be changed
时间窗: After 90 days level of fatigue will be measured
Level of fatigue: Modified Borg Scale If the fatigue score decreases,it means better outcome, If the fatigue score increases,it means outcome is worse
Exercise Tolerance Exercise tolerance variables •Six Minute Walk Distance[6MWD (meter) ]will be changed
时间窗: After 90 days 6MWD will be measured
Exercise tolerance variables • Six Minute Walk Distance \[6MWD (meter) \] minimum 350m in 6minute at a time(without taking any rest) is standard.The more the distance,the more the better outcome.
Exercise Tolerance variables • Level of Dyspnea : Modified Borg Scale will be changed
时间窗: After 90 days level of Dyspnea will be measured
Level of Dyspnea : Modified Borg Scale If the dyspnea score decreases,it means better outcome If the dyspnea score increases,it means outcome is worse
次要结局
未报告次要终点
研究者
Samia Hassan
Principal investigator
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh