- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06952647
Hematological and Metabolic Markers in Carpal Tunnel Syndrome
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, but the severity of symptoms experienced by patients does not always correspond to abnormalities detected by nerve conduction studies. This prospective cross-sectional study investigates whether routinely available metabolic, hematological, and inflammatory markers are associated with CTS and with patient-reported symptom and functional burden.
Adults referred for evaluation of suspected CTS were enrolled. Participants with electrodiagnostically confirmed CTS were compared with symptomatic individuals whose nerve conduction studies were normal. Clinical findings, Boston Carpal Tunnel Questionnaire scores, electrophysiological severity, and blood-based metabolic and inflammatory measures were evaluated. The study aims to better understand whether systemic metabolic and inflammatory factors contribute to the clinical expression of CTS beyond the degree of large-fiber nerve conduction abnormality.
Study Overview
Status
Conditions
Detailed Description
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and results from compression of the median nerve at the wrist. Although local mechanical compression is central to the disorder, the clinical presentation of CTS varies considerably. Patients with similar nerve conduction abnormalities may report very different levels of pain, paresthesia, weakness, and functional limitation. This variability suggests that systemic metabolic and inflammatory factors may contribute to the clinical expression of CTS in addition to the degree of median nerve conduction abnormality.
Several systemic conditions, including obesity, diabetes mellitus, thyroid disease, and inflammatory disorders, are associated with CTS. Obesity and metabolic dysfunction may increase peripheral nerve vulnerability through metabolic, vascular, and inflammatory mechanisms. Low-grade systemic inflammation has also been investigated as a possible contributor to CTS. Routinely available blood measurements may therefore provide additional information about systemic factors accompanying the disorder.
In recent years, several hematological indices derived from routine blood counts have been used as markers of systemic inflammatory activity. These include the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Metabolic and inflammation-related measures such as triglycerides, the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL), the C-reactive protein-to-albumin ratio (CAR), and the C-reactive protein-albumin-lymphocyte (CALLY) index may also reflect different aspects of systemic metabolic and inflammatory burden.
This prospective cross-sectional study includes adults referred for electrodiagnostic evaluation because of symptoms suggestive of CTS. Participants with electrodiagnostically confirmed median neuropathy at the wrist constitute the CTS group, while symptomatic individuals with normal nerve conduction studies serve as the comparison group. This design allows systemic markers associated with confirmed median nerve involvement to be examined against a clinically relevant symptomatic reference group rather than against asymptomatic healthy volunteers.
Clinical examination and nerve conduction studies are performed according to the study protocol. In participants with confirmed CTS, symptom severity and functional status are assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Routine hematological, biochemical, metabolic, and inflammatory measurements are obtained from fasting blood samples, and derived inflammatory and metabolic indices are calculated from their component variables.
The study evaluates three related but distinct clinical domains: the presence of electrodiagnostically confirmed CTS, patient-reported symptom and functional burden, and electrodiagnostic severity. The main objective is to determine whether routinely available metabolic and inflammatory measures are associated differently with these domains. In particular, the study examines whether systemic metabolic or inflammatory factors may help explain differences in patient-reported burden that are not fully captured by conventional nerve conduction findings.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Altindag
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Ankara, Altindag, Turkey (Türkiye), 06230
- Department of Physical Therapy and Rehabilitation, University of Health Sciences, Ankara Training and Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age between 18-65 years
- Having undergone Electromyography (EMG) testing for Carpal Tunnel Syndrome (CTS)-like symptoms
- Recent complete blood count, C-Reactive Protein (CRP), and albumin available
Exclusion Criteria:
- Age below 18 or above 65 years
- Pregnancy
- History of wrist trauma or surgical operation
- Chronic kidney disease
- Gout
- Rheumatoid arthritis
- Connective tissue disease
- Thyroid disorders
- Acromegaly
- Polyneuropathy
- Thoracic outlet syndrome
- Brachial plexopathy
- Cervical disc herniation
- Presence of cardiac pacemaker
- Steroid use
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Electrodiagnostically Confirmed CTS Group
Adults with symptoms suggestive of carpal tunnel syndrome and electrodiagnostic evidence of median neuropathy at the wrist.
Participants were evaluated for clinical findings, patient-reported symptom and functional burden, electrodiagnostic severity, and fasting metabolic, hematological, and inflammatory measures.
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Symptomatic Electrodiagnostically Normal Control Group
Adults referred with symptoms suggestive of carpal tunnel syndrome but with normal nerve conduction studies.
Participants were evaluated using the same clinical and fasting metabolic, hematological, and inflammatory measures as the CTS group and served as the symptomatic comparison group.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Evaluation of Systemic Inflammation Response Index (SIRI) as an Inflammatory Marker
Time Frame: up to 4 weeks
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The systemic inflammation response index (SIRI) is calculated as neutrophil count × monocyte count / lymphocyte count. It reflects the combined effect of neutrophil and monocyte-driven innate immunity versus lymphocyte-mediated adaptive immunity. SIRI has been proposed as a robust marker of inflammation in several chronic diseases. In the current study, SIRI was evaluated in individuals with and without Carpal Tunnel Syndrome (CTS) to investigate its potential as an indicator of inflammatory burden. |
up to 4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Evaluation of Platelet/Lymphocyte Ratio (PLR) as an Inflammatory Marker
Time Frame: up to 4 weeks
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Platelet/lymphocyte ratio (PLR) is another hematological marker that reflects systemic inflammation. During inflammatory responses, platelet counts often increase while lymphocyte counts decrease, resulting in an elevated PLR. Platelets play an active role in inflammation by releasing inflammatory mediators and interacting with leukocytes. PLR, calculated from routine blood tests, has been increasingly used in the assessment of inflammatory conditions. In this study, PLR values were compared between patients with Carpal Tunnel Syndrome (CTS) and healthy controls to evaluate its association with inflammation in CTS. |
up to 4 weeks
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Evaluation of Monocyte/Lymphocyte Ratio (MLR) as an Inflammatory Marker
Time Frame: up to 4 weeks
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Monocyte/lymphocyte ratio (MLR) is a peripheral blood marker used to assess systemic inflammatory status. Monocytes contribute to chronic inflammation and tissue remodeling, while lymphocytes are typically reduced in inflammatory states. An increased MLR may reflect an enhanced inflammatory response. Like other ratios, MLR can be easily derived from complete blood count parameters. In this study, MLR was analyzed in patients with and without Carpal Tunnel Syndrome (CTS) to explore its relevance as a potential inflammatory biomarker. |
up to 4 weeks
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Evaluation of Neutrophil/Lymphocyte Ratio (NLR) as an Inflammatory Marker
Time Frame: up to 4 weeks
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In inflammatory diseases, the immune response often leads to an increase in circulating neutrophils and a decrease in lymphocytes, resulting in an elevated neutrophil/lymphocyte ratio (NLR). This parameter has recently gained attention as a simple, cost-effective, and readily available marker of systemic inflammation. NLR is derived from routine complete blood count tests and reflects the balance between innate (neutrophils) and adaptive (lymphocytes) immune responses. In the present study, NLR was compared between patients with Carpal Tunnel Syndrome (CTS) and healthy controls to investigate its potential role as a marker of inflammation in CTS. |
up to 4 weeks
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Evaluation of Systemic Immune-inflammation Index (SII) as an Inflammatory Marker
Time Frame: up to 4 weeks
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The systemic immune-inflammation index (SII) is a composite marker calculated using the formula: platelet count × neutrophil count / lymphocyte count. It simultaneously incorporates three types of immune cells and is considered a more comprehensive indicator of the systemic inflammatory status. Elevated SII levels have been associated with various inflammatory and immune-mediated conditions. In this study, SII values were compared between CTS patients and healthy controls to assess its potential utility in identifying inflammatory activity in CTS. |
up to 4 weeks
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- Comparison of C-Reactive Protein levels (CRP) and CALLY
Time Frame: up to 4 weeks
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- Comparison of C-Reactive Protein levels (CRP) levels between case and control groups.
CRP is an acute phase protein used as an inflammatory marker.
CRP's half-life is approximately 19 hours, making it a responsive marker that can indicate both the onset of inflammation and the response to treatment relatively quickly.
CALLY (C-reactive protein-Albumin-Lymphocyte) index is a composite scoring system that integrates CRP, albumin, and lymphocyte count to reflect both inflammatory status and nutritional-immune condition simultaneously.
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up to 4 weeks
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Comparison of TG/HDL
Time Frame: up to 4 weeks
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Comparison of TG/HDL between case and control groups
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up to 4 weeks
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Evaluation of Electrodiagnostic Severity of Carpal Tunnel Syndrome
Time Frame: up to 4 weeks
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Electromyography (EMG) is part of electrodiagnostic assessment used to evaluate peripheral nerve and muscle function. In this study, carpal tunnel syndrome severity was classified based on nerve conduction study findings as follows:
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up to 4 weeks
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Collaborators and Investigators
Investigators
- Principal Investigator: Nadide Koca, M.D., University of Health Sciences, Ankara Training and Research Hospital, TURKEY
Publications and helpful links
General Publications
- Newington L, Harris EC, Walker-Bone K. Carpal tunnel syndrome and work. Best Pract Res Clin Rheumatol. 2015 Jun;29(3):440-53. doi: 10.1016/j.berh.2015.04.026. Epub 2015 May 27.
- Werner RA, Andary M. Carpal tunnel syndrome: pathophysiology and clinical neurophysiology. Clin Neurophysiol. 2002 Sep;113(9):1373-81. doi: 10.1016/s1388-2457(02)00169-4.
- Otelea MR, Nartea R, Popescu FG, Covaleov A, Mitoiu BI, Nica AS. The Pathological Links between Adiposity and the Carpal Tunnel Syndrome. Curr Issues Mol Biol. 2022 Jun 8;44(6):2646-2663. doi: 10.3390/cimb44060181.
- Malakootian M, Soveizi M, Gholipour A, Oveisee M. Pathophysiology, Diagnosis, Treatment, and Genetics of Carpal Tunnel Syndrome: A Review. Cell Mol Neurobiol. 2023 Jul;43(5):1817-1831. doi: 10.1007/s10571-022-01297-2. Epub 2022 Oct 10.
- Tonga F, Bahadir S. The Factors Associated with Carpal Tunnel Syndrome Severity. Turk Neurosurg. 2022;32(3):392-397. doi: 10.5137/1019-5149.JTN.34519-21.2.
- Zvonickova K, Rhee A, Sandy-Hindmarch O, Furniss D, Wiberg A, Schmid AB. Systemic low-grade C-reactive protein is associated with proximal symptom spread in carpal tunnel syndrome. Pain Rep. 2024 Apr 10;9(3):e1156. doi: 10.1097/PR9.0000000000001156. eCollection 2024 Jun.
- Gunes M, Buyukgol H. Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratios with the severity of idiopathic carpal tunnel syndrome. Muscle Nerve. 2020 Mar;61(3):369-374. doi: 10.1002/mus.26791. Epub 2020 Jan 9.
- Wang RH, Wen WX, Jiang ZP, Du ZP, Ma ZH, Lu AL, Li HP, Yuan F, Wu SB, Guo JW, Cai YF, Huang Y, Wang LX, Lu HJ. The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage. Front Immunol. 2023 Feb 13;14:1115031. doi: 10.3389/fimmu.2023.1115031. eCollection 2023.
- Padua L, Cuccagna C, Giovannini S, Coraci D, Pelosi L, Loreti C, Bernabei R, Hobson-Webb LD. Carpal tunnel syndrome: updated evidence and new questions. Lancet Neurol. 2023 Mar;22(3):255-267. doi: 10.1016/S1474-4422(22)00432-X. Epub 2022 Dec 13.
- Joshi A, Patel K, Mohamed A, Oak S, Zhang MH, Hsiung H, Zhang A, Patel UK. Carpal Tunnel Syndrome: Pathophysiology and Comprehensive Guidelines for Clinical Evaluation and Treatment. Cureus. 2022 Jul 20;14(7):e27053. doi: 10.7759/cureus.27053. eCollection 2022 Jul.
- Che X, Chen Q, He D, Fan L. Correlation of CRP/Albumin ratio and low serum albumin with the risk of major adverse cardiovascular events in elderly patients with chronic total occlusion. Hereditas. 2025 Dec 29;163(1):19. doi: 10.1186/s41065-025-00622-1.
- Razavi AS, Karimi N, Bashiri F. The relationship of serum lipid profiles and obesity with the severity of carpal tunnel syndrome. Pan Afr Med J. 2021 Jun 1;39:90. doi: 10.11604/pamj.2021.39.90.27234. eCollection 2021.
- Yano K, Kawabata A, Ikeda M, Suzuki K, Kaneshiro Y, Egi T. Hypercholesterolemia Is Associated with the Subjective Evaluation of Postoperative Outcomes in Patients with Idiopathic Carpal Tunnel Syndrome Who Undergo Surgery: A Multivariate Analysis. Plast Reconstr Surg. 2018 Apr;141(4):941-948. doi: 10.1097/PRS.0000000000004228.
- Zhu D, Lin YD, Yao YZ, Qi XJ, Qian K, Lin LZ. Negative association of C-reactive protein-albumin-lymphocyte index (CALLY index) with all-cause and cause-specific mortality in patients with cancer: results from NHANES 1999-2018. BMC Cancer. 2024 Dec 5;24(1):1499. doi: 10.1186/s12885-024-13261-y.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AnkaraTRH-FTR-NK-04
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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