The Swedish Spinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA)

The main aim of this study is to gain an in-depth knowledge of cardiopulmonary and autonomic health consequences, and related risk factors among people with long-term high-level spinal cord injury. The result of this study will form the basis for further research to improve prevention strategies and risk prediction of cardiopulmonary disorders in people with spinal cord injury.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Spinal Cord Injuries; Pulmonary Disease; Autonomic Dysfunction

Detailed Description

Life expectancy for people with spinal cord injury (SCI) has increased during the 20th century as a result of improvements in health care systems and the environment. The incidence of SCI is stable and as a consequence the prevalence of SCI has increased globally leading to a growing population of persons aging with SCI. Therefore, SCI research need to focus on the physiology of aging to prevent premature cardiovascular and pulmonary diseases, which are the leading causes of death.

The disruption of sensory-, motor- and autonomic pathways causes major neurological deficits which alter the physiologic conditions. Among people with SCI above the mid-thoracic level dysfunction in pulmonary, autonomic cardiovascular regulation and emerging metabolic cardiovascular risk factors are well-known. In addition, paralysis of the abdominal and thoracic musculature causes restrictive pulmonary dysfunction, weak cough and atelectasis contributing to the mortality in SCI.

Cardiovascular disease (CVD) is more prevalent and occurs earlier in life among people with SCI compared to the general population. The increased prevalence of traditional risk factors cannot, however, fully explain these findings. Cardiovascular autonomic dysfunction has been hypothesized to contribute to the increased risk. The need for advances in risk management is therefore important as the first symptoms of coronary atherosclerosis are commonly sudden death or acute coronary syndrome. This is further complicated by the sensory loss and reduced ability to perform strenuous activities leading to asymptomatic disease as typical symptoms of exertional angina pectoris does not manifest. Risk assessment tools, such as Framingham risk score or Systematic Coronary Risk Evaluation (SCORE), are available but lack the precision in people with SCI as these tools are calibrated on the general population.

The Swedish Spinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment - SPICA - was initiated to assess the effects of aging with SCI on the cardiovascular, pulmonary and autonomic systems in a cohort of middle-aged persons with long-term SCI. SPICA combines advanced imaging techniques, likely to play an important role in risk stratification of CVD and pulmonary disease in the future, with functional analyses, and generic and SCI-specific assessment tools.

The overarching aim of SPICA is to assess and extensively characterize the cardiopulmonary and autonomic health status in middle-aged persons with a severe and high-level SCI. The study will elucidate the cardiopulmonary health consequences specific to persons living with a SCI through comparison of results to matched controls. The results of SPICA will advance the investigator's knowledge in this field and thereby improve prevention strategies and risk prediction of CVD and pulmonary disorders in people with SCI.

• Study Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden
    • Rehabilitation medicine Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The total SCI population matching the inclusion criteria in Skåne, Sweden (n=38).

Description

Inclusion criteria:

• Traumatic SCI
• SCI duration >5 years
• Neurological level of lesion C1-T6
• ASIA Impairment Scale A-C
• Resident in Skåne, Sweden
• No dependency of full-time ventilation support

Control group will consist of matched controls from the Swedish Cardiopulmonary and Bioimage Study's data of the general population.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Persons with Spinal cord injury (SCI); The total population of a specified group of persons with traumatic SCI will be invited to participate.
Matched control group; A matched control group of the general population at a ratio of 3-4 to each person with SCI will be recruited from the Swedish Cardiopulmonary and Bioimage Study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary artery calcium score	Measures the amount of calcium in the coronary arteries from computed tomography imaging. Scores from 0 to >1000, a higher value represents a worse outcome. Value >0 indicates coronary atherosclerosis.	Day 1
Intima media thickness in the carotid arteries	Ultrasound of carotid arteries to measure intima media thickness	Day 1
Assesses atherosclerosis in the coronary arteries	Coronary CT Angiography	Day 1
Prevalence of structural changes in the lung tissue	High resolution CT scan	Day 1
Ectopic fat distribution	CT body composition of epicardium, liver, abdomen and muscle	Day 1
Heart rate response to deep breathing	Measures electrocardiography the activity of the autonomic nervous system based on the time and frequency domain indices of heart rate variability during deep breathing.	Day 1
Orthostatic blood pressure	Measures systolic and diastolic blood pressure changes from supine position and after 3 minutes in seating position.	Day 1
Plaques in the carotid arteries	Ultrasound of carotid arteries to measure and characterize plaques.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Questionnaire	self-reported health, lifestyle, social determinants, living conditions and medical history	Day 1
Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET)	Self-reported spasticity scale that measures the impact of spasticity in activities of daily living. Ranges from -105 to 105. Low values represents a worse outcome	Day 1
Sense of Coherence Scale (SOC-13)	To assess the 3 dimensions of the SOC concept: comprehensibility (5 items), manageability (4 items), and meaningfulness (4 items). Value ranges from 13 to 91 and low values represent a worse outcome.	Day 1
Hospital Anxiety and Depression Scale (HADS)	Screening instrument for anxiety and depression. Consists of two subscales, one for depression and one for anxiety each ranging from 0-21, high value represents a worse outcome.	Day 1
Spinal Cord Independence Measure (SCIM III)	SCIM III comprises 19 areas of activities of daily living grouped into 3 subscales: self-care, respiratory and sphincter management, and mobility and measure self-reported activity limitation. SCIM III ranges from 0-100 and a low value represents a worse outcome.	Day 1
Modified Ashworth Scale	Clinical examination of spasticity in specific muscles of the upper and lower extremities. The scale ranges from 0-4 with increasing scores indicating increased spasticity.	Day 1
American Spinal Injury Association (ASIA) Impairment Scale	Measures the extent of spinal cord injury and the neurological level of injury. The extent of injury is classified as A-E. A (complete injury); B (sensory incomplete injury); C (motor incomplete injury, more than half of key muscle functions below the neurological level have a muscle grade 2 or less); D (motor incomplete injury, at least half of key muscle functions below the neurological level have a muscle grade 3 or more); E (normal sensory and motor function). i.e. from complete to normal neurological function. Thus A represents a worse outcome than E. The neurological level of injury reflects the most rostral spinal cord level with normal sensory and motor function.	Day 1
Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI)	Measures the occurrence and severity of autonomic dysreflexia (AD) and hypotension in spinal cord injury. Consists of two subscales ranging from 0-204 (AD) and 0-232 (hypotension) and a high value represents a worse outcome.	Day 1
Total cholesterol	Analysis of venous blood sample for total cholesterol levels	Day 1
High density lipoproteins (HDL)	Analysis of venous blood sample for total HDL-levels	Day 1
Low density lipoproteins (LDL)	Analysis of venous blood sample for LDL-levels	Day 1
Triglycerides	Analysis of venous blood sample for triglycerides levels	Day 1
Fasting plasma glucose	Analysis of venous blood sample for fasting plasma glucose level	Day 1
Glycated hemoglobin (HbA1c)	Analysis of venous blood sample for HbA1c level	Day 1
high sensitive C-reactive protein (hsCRP)	Analysis of venous blood sample for hsCRP level	Day 1
Cystatin C	Analysis of venous blood sample for Cystatin C level	Day 1
Creatinine	Analysis of venous blood sample for Creatinine level	Day 1
Urate	Analysis of venous blood sample for Urate level	Day 1
Hemoglobin	Analysis of venous blood sample for Hemoglobin level	Day 1
Erythrocytes	Analysis of venous blood sample for erythrocytes level	Day 1
Erythrocyte volume fraction (EVF)	Analysis of venous blood sample for EVF level	Day 1
Leukocytes	Analysis of venous blood sample for leukocytes level	Day 1
Trombocytes	Analysis of venous blood sample for trombocytes level	Day 1
Erythrocytes Mean Corpuscular Hemoglobin (Erc-MCH)	Analysis of venous blood sample for Erc-MCH level	Day 1
Erythrocytes Mean Corpuscular Volume (Erc-MCV)	Analysis of venous blood sample for Erc-MCV level	Day 1
Neutrophils	Analysis of venous blood sample for neutrophils level	Day 1
Eosinophils	Analysis of venous blood sample for Eosinophils level	Day 1
Basophils	Analysis of venous blood sample for Basophils level	Day 1
Lymphocytes	Analysis of venous blood sample for lymphocytes level	Day 1
Monocytes	Analysis of venous blood sample for monocytes level	Day 1
Absolute glomerular filtration rate (GFR)	Calculated absolute GFR from Cystatin C level, body height, body weight, age and gender.	Day 1
Body weight	Recorded in kilograms with a portable scale for wheelchairs.	Day 1
Body height	Recorded in centimeters in supine position using a flexible measure tape	Day 1
Waist circumference	Recorded in centimeters in supine position using a flexible measure tape	Day 1
Hip circumference	Recorded in centimeters in supine position using a flexible measure tape	Day 1
Body mass index	Produced by dividing the body weight in kilograms with the body height in meters to the power of two	Day 1
Accelerometry	Measures ambulatory activity for seven days	Seven days
Resting blood pressure	Standard resting systolic and diastolic blood pressure	Day 1
Ankle-brachial index	Measures atherosclerosis in the lower extremities by dividing the systolic blood pressure at the ankle with the systolic blood pressure of the arm.	Day 1
Ambulatory 24-hour blood pressure	Monitors systolic and diastolic blood pressures every 30 minutes over 24 hours	Day 1
Electrocardiography	Standard 12-lead ECG recording	Day 1
24-hour Holter-ECG	Monitors the heart activity	Day 1
Advanced glycation endproduct (AGE)	Measures AGE in the skin	Day 1
Spirometry	Dynamic spirometry	Day 1
Gas diffusing capacity (DLCO)	Measures diffusing capacity of the lungs using the single breath method	Day 1
Impulse oscillometry	Measures lung mechanics	Day 1
Arterial stiffness	Estimated by pulse wave analysis	Day 1
Arterial stiffness	Measured using pulse wave velocity	Day 1

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Skane University Hospital

Publications and helpful links

General Publications

• Devivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012 May;50(5):365-72. doi: 10.1038/sc.2011.178. Epub 2012 Jan 24.
• Groah SL, Charlifue S, Tate D, Jensen MP, Molton IR, Forchheimer M, Krause JS, Lammertse DP, Campbell M. Spinal cord injury and aging: challenges and recommendations for future research. Am J Phys Med Rehabil. 2012 Jan;91(1):80-93. doi: 10.1097/PHM.0b013e31821f70bc.
• Warburton DE, Eng JJ, Krassioukov A, Sproule S; the SCIRE Research Team. Cardiovascular Health and Exercise Rehabilitation in Spinal Cord Injury. Top Spinal Cord Inj Rehabil. 2007 Summer;13(1):98-122. doi: 10.1310/sci1301-98.
• Schilero GJ, Radulovic M, Wecht JM, Spungen AM, Bauman WA, Lesser M. A center's experience: pulmonary function in spinal cord injury. Lung. 2014 Jun;192(3):339-46. doi: 10.1007/s00408-014-9575-8. Epub 2014 Apr 11.
• Bergstrom G, Berglund G, Blomberg A, Brandberg J, Engstrom G, Engvall J, Eriksson M, de Faire U, Flinck A, Hansson MG, Hedblad B, Hjelmgren O, Janson C, Jernberg T, Johnsson A, Johansson L, Lind L, Lofdahl CG, Melander O, Ostgren CJ, Persson A, Persson M, Sandstrom A, Schmidt C, Soderberg S, Sundstrom J, Toren K, Waldenstrom A, Wedel H, Vikgren J, Fagerberg B, Rosengren A. The Swedish CArdioPulmonary BioImage Study: objectives and design. J Intern Med. 2015 Dec;278(6):645-59. doi: 10.1111/joim.12384. Epub 2015 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: April 21, 2018
• First Posted (Actual): May 3, 2018

Study Record Updates

• Last Update Posted (Actual): May 14, 2019
• Last Update Submitted That Met QC Criteria: May 11, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Rehabilitation; Epidemiology; Middle aged; Clinical protocols
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Cardiovascular Diseases; Wounds and Injuries; Spinal Cord Injuries; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: 2017-0765

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