Impact of Vitamin D3 Administration on Cardiac Autonomic Tone in Asthma Chronic Obstructive Pulmonary Disease(COPD) Overlap Patients

NCT03773809 | Completed DMC

• 1 other identifier: No. BSMMU/2018/478
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Title:Impact of vitamin D administration on cardiac autonomic tone in Asthma Chronic Obstructive Pulmonary Disease (COPD) Overlap patients: A blinded randomized control trial. Background: Respiratory disease is closely associated with cardiovascular disease. Reduced Heart Rate Variability (HRV), reflecting impaired autonomic activity have been reported in both asthma and COPD. Vitamin D deficiency is a common feature in Asthma COPD Overlap (ACO) patient. Relationship between vitamin D deficiency and low HRV has been reported. Vitamin D administration has been reported to improve cardiac autonomic modulation in healthy subjects in response to external stressor. Objective: To assess the changes in cardiac autonomic tone after vitamin D administration for 90 days in vitamin D deficient ACO patients. Hypothesis:Null: Vitamin D administration does not have impact on cardiac autonomic tone in vitamin D3 deficient ACO patient. .Method: This randomized controlled trial will be conducted by Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from September' 2017 to August' 2018. For this study, a total number of 60 subjects (age \> 40 years, both male and female) will be randomly selected. 30 diagnosed vitamin D deficient Asthma COPD Overlap (ACO) patients will form group A and another 30 diagnosed vitamin D3 deficient ACO patients with similar age, sex, (Body Mass Index) BMI will constitute control group B. Patients of study group B0 will take vitamin D3 with a prescribed schedule for 3 months and followed up after 3 months (group B90). On the other hand patients of group A1 will be given placebo and followed up after 3 months (group A90). All these patients will continue their medication prescribed by physician during these 3 months. On the basis of data recording - group B1 and group B90 will constitute pre and post vitamin D group whereas group A0 and group A90 will represent pre and post placebo follow up at day 0 and day 90. Cardiac autonomic nerve function will be assessed by recording ECG \& Heart Rate Variability (HRV) analysis by a data acquisition device, powerlab 8/35, AD instruments, Australia. HRV measures of all patients will be recorded at baseline.Then after 3 months of follow up it will be recorded in both groups at day 90. Serum 25(OH)D level will be measured of all subject at day 0 and day 90. For statistical analysis unpaired and paired "t" test will be done by using Microsoft Office Excel Word version 2016

Conditions

Asthma-COPD Overlap Syndrome; Vitamin D Deficiency; Cardiac Autonomic Tone

Keywords

ACO; HRV; Vitamin D deficiency

Outcome Measures

Primary Outcomes (14)

• vitamin D concentration

  serum vitamin D level was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Serum vitamin D level at 90 days

• Mean R-R interval in milliseconds

  Mean R-R interval was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Mean R-R interval at 90 days

• Mean Heart Rate in beats/min

  Mean Heart Rate was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Mean Heart Rate at 90 days

• Standard deviation of RR interval (SDRR) in milliseconds

  Standard deviation of RR interval (SDRR) was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Standard deviation of RR interval (SDRR) at 90 days

• Coefficient of variation of all the R-R interval (CVRR)

  Coefficient of variation of all the R-R interval (CVRR) was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Coefficient of variation of all the R-R interval (CVRR) at 90 days

• Square root of the mean squared differences of successive RR interval (RMSSD) in milliseconds

  Square root of the mean squared differences of successive RR interval (RMSSD) was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Square root of the mean squared differences of successive RR interval (RMSSD) at 90 days

• Standard deviation of successive RR interval differences between adjacent RR intervals (SDSD) in milliseconds

  Standard deviation of successive RR interval differences between adjacent RR intervals (SDSD) was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Standard deviation of successive RR interval differences between adjacent RR intervals (SDSD) at 90 dayss

• Number of RR interval differing by >50 milliseconds from adjacent intervals divided by the total number of all RR intervals (pRR50%) in %

  Number of RR interval differing by \>50 milliseconds from adjacent intervals divided by the total number of all RR intervals (pRR50%) was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Number of RR interval differing by >50 milliseconds from adjacent intervals divided by the total number of all RR intervals (pRR50%) at 90 days

• Total power (absolute) in frequency domain parameters of heart rate variability

  Total power (absolute) in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Total power (absolute) in frequency domain parameters of heart rate variability at 90 months

• Low Frequency (LF) power (absolute) in frequency domain parameters of heart rate variability

  Low Frequency (LF) power (absolute) in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Low Frequency (LF) power (absolute) in frequency domain parameters of heart rate variability at 90 days

• High Frequency (HF) power (absolute) in frequency domain parameters of heart rate variability

  High Frequency (HF) power (absolute) in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline High Frequency (HF) power (absolute) in frequency domain parameters of heart rate variability at 90days

• Low Frequency (LF) power in normalised units (n.u) in frequency domain parameters of heart rate variability

  Low Frequency (LF) power in normalised units (n.u) in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Low Frequency (LF) power in normalised units (n.u) in frequency domain parameters of heart rate variability at 90 days

• High Frequency (HF) power in normalised units (n.u) in frequency domain parameters of heart rate variability

  High Frequency (HF) power in normalised units (n.u) in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline High Frequency (HF) power in normalised units (n.u) in frequency domain parameters of heart rate variability at 90 days

• Ratio of Low frequency to High Frequency (HF) power in frequency domain parameters of heart rate variability

  Ratio of Low frequency to High Frequency (HF) power in frequency domain parameters of heart rate variability was measured at day 0 and after 90 days of vitamin D and placebo administration in vitamin D and in placebo group respectively

  Change from Baseline Ratio of Low frequency to High Frequency (HF) power in frequency domain parameters of heart rate variability at 90 days

Study Arms (4)

Group A0

PLACEBO COMPARATOR

Vitamin D3 deficient ACO patients with placebo at day 0.

Other: placebo

Group A90

PLACEBO COMPARATOR

Vitamin D3 deficient ACO patients with placebo at day 90.

Other: placebo

Group B0

ACTIVE COMPARATOR

Vitamin D3 deficient ACO patients with vitamin D3 at day 0.

Other: Vitamin D capsule

Group B90

ACTIVE COMPARATOR

Vitamin D3 deficient ACO patients with vitamin D3 at day 90.

Other: Vitamin D capsule

Interventions

Vitamin D capsule OTHER

The intervention was given by oral administration of vitamin D3 capsule each of which contains 40000 IU of vitamin D3. The capsule was manufactured and supplied by Beximco Pharmaceutical Limited, Bangladesh. The placebo was also be manufactured and supplied by the same pharmaceutical company and was similar in size shape \& appearance to vitamin D3 capsule but contained all the ingredients of vitamin D capsule other than the vitamin D3

Also known as: oral administration of Vitamin D capsule

Group B0; Group B90

placebo OTHER

oral administration of placebo

Group A0; Group A90

Eligibility Criteria

• Age: 40 Years - 80 Years
• Gender Eligibility Details: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 40-80 years of age
• Male
• Middle class of socioeconomic condition:.
• Stable patients of Asthma COPD Overlap (ACO) with \>4 years of disease duration.
• Vitamin D deficient (Serum 25-hydroxycholecalciferol, 25(OH)D level \< 30 ng/ml).
• Normal serum Ca+and inorganic phosphate level.
• Hypertension with ACO.
• Diabetes with ACO

You may not qualify if:

• Unstable patients with ACO (patients with exacerbation and medication changes in the past 30 days)
• With acute exacerbation of any pulmonary diseases, such as,
• Bronchial asthma
• Acute respiratory tract infection
• Current tuberculosis
• Pleural effusion
• Emphysematous bullae
• Interstitial lung disease
• Pneumonectomy or pulmonary lobectomy
• Pulmonary fibrosis.
• With acute exacerbation of any cardiac disease, like -
• Unstable angina pectoris
• Congestive heart failure
• Myocardial infarction
• Cardiac arrhythmia

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead

Study Sites (1)

Dr Sultana Ferdousi

Dhaka, 1200, Bangladesh

Location

Related Publications (24)

• Visweswaran RK, Lekha H. Extraskeletal effects and manifestations of Vitamin D deficiency. Indian J Endocrinol Metab. 2013 Jul;17(4):602-10. doi: 10.4103/2230-8210.113750.

  PMID: 23961475 BACKGROUND

• Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003 May;26(5):1553-79. doi: 10.2337/diacare.26.5.1553.

  PMID: 12716821 BACKGROUND

• Shaffer F, McCraty R, Zerr CL. A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability. Front Psychol. 2014 Sep 30;5:1040. doi: 10.3389/fpsyg.2014.01040. eCollection 2014.

  PMID: 25324790 BACKGROUND

• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

  PMID: 8598068 BACKGROUND

• Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6.

  PMID: 21646368 BACKGROUND

• Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, [Internet]. c2018. GOLD [updated 201; cited 2018 March 12] Available from: www.ginasthma.org

  BACKGROUND

• Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and Asthma-COPD Overlap (ACO) [Internet]. A joint project of GINA and GOLD [updated April 2017; Cited 2017 Nov 12]. Available from: www.msc.es/organizacion/sns/plan CalidadSNS/pdf/GOLD_ACOS_2017.pdf

  BACKGROUND

• Zupanic E, Zivanovic I, Kalisnik JM, Avbelj V, Lainscak M. The effect of 4-week rehabilitation on heart rate variability and QTc interval in patients with chronic obstructive pulmonary disease. COPD. 2014 Dec;11(6):659-69. doi: 10.3109/15412555.2014.898046. Epub 2014 Apr 30.

  PMID: 24787632 RESULT

• Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008 Jan 29;117(4):503-11. doi: 10.1161/CIRCULATIONAHA.107.706127. Epub 2008 Jan 7.

  PMID: 18180395 RESULT

• Wang L, Song Y, Manson JE, Pilz S, Marz W, Michaelsson K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C, Eaton CB, May HT, Anderson JL, Sesso HD. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012 Nov;5(6):819-29. doi: 10.1161/CIRCOUTCOMES.112.967604. Epub 2012 Nov 13.

  PMID: 23149428 RESULT

• Voss A, Schulz S, Schroeder R, Baumert M, Caminal P. Methods derived from nonlinear dynamics for analysing heart rate variability. Philos Trans A Math Phys Eng Sci. 2009 Jan 28;367(1887):277-96. doi: 10.1098/rsta.2008.0232.

  PMID: 18977726 RESULT

• Vitamin D council. I tested my vitamin D level. What do my result mean? 2017 [Internet]. [Cited 2017 Oct 25]. Available from: https://www.vitamindcouncil.org/i-tested-my-vitamin-d-levelwhat-do-result-mean/

  RESULT

• Odler B, Ivancso I, Somogyi V, Benke K, Tamasi L, Galffy G, Szalay B, Muller V. Vitamin D deficiency is associated with impaired disease control in asthma-COPD overlap syndrome patients. Int J Chron Obstruct Pulmon Dis. 2015 Sep 24;10:2017-25. doi: 10.2147/COPD.S91654. eCollection 2015.

  PMID: 26451099 RESULT

• Nalbant A, Vatan MB, Varim P, Varim C, Kaya T, Tamer A. Does Vitamin D Deficiency Effect Heart Rate Variability in Low Cardiovascular Risk Population? Open Access Maced J Med Sci. 2017 Mar 22;5(2):197-200. doi: 10.3889/oamjms.2017.041. eCollection 2017 Apr 15.

  PMID: 28507628 RESULT

• Mann MC, Hollenberg MD, Hanley DA, Ahmed SB. Vitamin D, the autonomic nervous system, and cardiovascular risk. Physiol Rep. 2015 Apr;3(4):e12349. doi: 10.14814/phy2.12349. No abstract available.

  PMID: 25902783 RESULT

• Mann MC, Exner DV, Hemmelgarn BR, Turin TC, Sola DY, Ellis L, Ahmed SB. Vitamin D supplementation is associated with improved modulation of cardiac autonomic tone in healthy humans. Int J Cardiol. 2014 Mar 15;172(2):506-8. doi: 10.1016/j.ijcard.2014.01.058. Epub 2014 Jan 23. No abstract available.

  PMID: 24502876 RESULT

• Lutfi MF. Autonomic modulations in patients with bronchial asthma based on short-term heart rate variability. Lung India. 2012 Jul;29(3):254-8. doi: 10.4103/0970-2113.99111.

  PMID: 22919165 RESULT

• Hsu CH, Tsai MY, Huang GS, Lin TC, Chen KP, Ho ST, Shyu LY, Li CY. Poincare plot indexes of heart rate variability detect dynamic autonomic modulation during general anesthesia induction. Acta Anaesthesiol Taiwan. 2012 Mar;50(1):12-8. doi: 10.1016/j.aat.2012.03.002. Epub 2012 Apr 3.

  PMID: 22500908 RESULT

• Habib GMM, Nahar K, Habib F. Prevalence of Asthma and COPD Overlapping Syndrome (ACOS) in a busy primary care setting of Bangladesh. 1st IPCRG South Asian Scientific Conference: 2017 3-5 Agaust; Colombo. sri Lanka

  RESULT

• DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol. 2013 Aug;39(5):458-84. doi: 10.1111/nan.12020.

  PMID: 23336971 RESULT

• Burt MG, Mangelsdorf BL, Stranks SN, Mangoni AA. Relationship between Vitamin D Status and Autonomic Nervous System Activity. Nutrients. 2016 Sep 13;8(9):565. doi: 10.3390/nu8090565.

  PMID: 27649235 RESULT

• Brzostek D, Kokot M. Asthma-chronic obstructive pulmonary disease overlap syndrome in Poland. Findings of an epidemiological study. Postepy Dermatol Alergol. 2014 Dec;31(6):372-9. doi: 10.5114/pdia.2014.47120. Epub 2014 Dec 3.

  PMID: 25610352 RESULT

• Bai JW, Mao B, Yang WL, Liang S, Lu HW, Xu JF. Asthma-COPD overlap syndrome showed more exacerbations however lower mortality than COPD. QJM. 2017 Jul 1;110(7):431-436. doi: 10.1093/qjmed/hcx005.

  PMID: 28100824 RESULT

• Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981 Jul 10;213(4504):220-2. doi: 10.1126/science.6166045.

  PMID: 6166045 RESULT

MeSH Terms

Conditions

Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome; Vitamin D Deficiency

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• SULTANA FERDOUSI, FERDOUSI

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both the patients and the principal investigator will remain blind to the intervention given. After the end of follow up, at the time of data analysis principal investigator will be provided with the information about which patient isgoven placebo and which patient isgivev drug.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident

Model Details: Baseline group: This group will include 60 vitamin D3 deficient ACO patients. Group A: Group A0: Vitamin D3 deficient ACO patients with placebo at day 0. Group A90: Vitamin D3 deficient ACO patients with placebo at day 90 Group B: Group B0: Vitamin D3 deficient ACO patients with vitamin D3 at day 0. Group B90: Vitamin D3 deficient ACO patients with vitamin D3 at day 90. All the patients will be similar by age, sex and BMI

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 12, 2018
• Study Start: August 1, 2017
• Primary Completion: June 30, 2018
• Study Completion: August 31, 2018
• Last Updated: December 12, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)