Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Neck Pain

Neck Pain Clinical Trial

Official title:

Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Patients With Chronic Nonspecific Neck Pain: Study Protocol for a Randomized Controlled Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05568394
• Other study ID #: FF-65 2301484
• Status: Completed
• Phase: N/A
• Start date: November 15, 2022
• Est. completion date: February 5, 2024

Study information

• Verified date: February 2024
• Source: Chiang Mai University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Structural brain alterations in pain-related areas have been demonstrated in patients with nonspecific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on brain imaging biomarkers in patients with chronic nonspecific neck pain. The secondary objectives are to assess neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength.

Description:

This study is a single-blinded, randomized controlled trial. Forty-eight participants with chronic nonspecific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (2 visits per week). The control group will receive routine physical therapy. Primary outcomes are brain imaging biomarkers (cortical gray matter: volume, thickness and area, and white matter: fractional anisotropy and mean diffusivity) in pain-related areas. Secondary outcomes are neurochemical biomarkers (N-acetylaspartate, NAA; creatine, Cr; glutamic acid/glutamine, Glu/Gln; myoinositol, mI; and choline, cho), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 5, 2024
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

• a history of nonspecific neck pain for = 3 months
• an average pain intensity over the past week = 35 mm. on a visual analogue scale (VAS)

Exclusion Criteria:

• a history of head and neck injury or surgery
• known or suspected vestibular pathology or dizziness caused by underlying pathology in the ear, brain and sensory nerve pathways (e.g. benign paroxysmal positional vertigo) and/or vascular disorders
• any neurological or musculoskeletal condition that could affect the outcomes (e.g., scoliosis, torticollis, myofascial pain syndrome, fibromyalgia and rheumatoid arthritis)
• metabolic conditions (e.g., diabetes, obesity (BMI > 30 kg/m2) and hypertension)
• psychological symptoms (e.g., anxiety, depression and schizophrenia)
• contraindications to MRI (e.g., pregnancy/breastfeeding, claustrophobia and ferromagnetic implants)
• receiving physiotherapy treatment for their neck conditions in the past 12 months.

Related Conditions & MeSH terms

• Neck Pain

Intervention

Other:
• Manual therapy combinded with therapeutic exercise
The treatment includes cervical mobilization and specific therapeutic exercises: craniocervical and cervical flexors and extensors, axioscapular muscles, and postural correction (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).
• Routine physical therapy
The treatment includes routine physical therapy (e.g., modalities, range of motion and/or gentle stretching exercise) (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).

Locations

Country	Name	City	State
Thailand	Department of Physical Therapy, Faculty of Associated Medical Sciences	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
Chiang Mai University

Country where clinical trial is conducted

Thailand, 

References & Publications (7)

Coppieters I, De Pauw R, Caeyenberghs K, Lenoir D, DeBlaere K, Genbrugge E, Meeus M, Cagnie B. Differences in white matter structure and cortical thickness between patients with traumatic and idiopathic chronic neck pain: Associations with cognition and pain modulation? Hum Brain Mapp. 2018 Apr;39(4):1721-1742. doi: 10.1002/hbm.23947. Epub 2018 Jan 11. — View Citation

de Zoete RMJ, Stanwell P, Weber KA, Snodgrass SJ. Differences in Structural Brain Characteristics Between Individuals with Chronic Nonspecific Neck Pain and Asymptomatic Controls: A Case-Control Study. J Pain Res. 2022 Feb 18;15:521-531. doi: 10.2147/JPR.S345365. eCollection 2022. — View Citation

Didehdar D, Kamali F, Yoosefinejad AK, Lotfi M. The effect of spinal manipulation on brain neurometabolites in chronic nonspecific low back pain patients: a randomized clinical trial. Ir J Med Sci. 2020 May;189(2):543-550. doi: 10.1007/s11845-019-02140-2. Epub 2019 Nov 26. — View Citation

Johnston V, O'Leary S, Comans T, Straker L, Melloh M, Khan A, Sjogaard G. A workplace exercise versus health promotion intervention to prevent and reduce the economic and personal burden of non-specific neck pain in office personnel: protocol of a cluster-randomised controlled trial. J Physiother. 2014 Dec;60(4):233; discussion 233. doi: 10.1016/j.jphys.2014.08.007. Epub 2014 Oct 11. — View Citation

Jull G, Falla D, Treleaven J, O'Leary S. Management of neck pain disorders: a research informed approach. Edinburgh: Elseiver Limited; 2019.

Maitland GD, Hengeveld E, Banks K, Anglaise K. Vertebral manipulation. 7th ed. Oxford: Butterworth-Heinemann: Elsevier; 2005.

Sremakaew M, Jull G, Treleaven J, Barbero M, Falla D, Uthaikhup S. Effects of local treatment with and without sensorimotor and balance exercise in individuals with neck pain: protocol for a randomized controlled trial. BMC Musculoskelet Disord. 2018 Feb 13;19(1):48. doi: 10.1186/s12891-018-1964-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortical gray matter: volume and thickness	Cortical gray matter (volume and thickness) will be measured in pain-related areas (thalamus, prefrontal cortex (PFC), primary somatosensory cortex (S1), primary motor cortex (M1), insula, cingulate cortex, precuneus, temporal lobe and periaqueductal gray matter) using a Magnetic resonance imaging (MRI) machine	At baseline and post-intervention
Secondary	Neurochemical biomarkers: N-acetylaspartate (NAA), creatine (Cr), glutamic acid/glutamine (Glu/Gln), myoinositol (mI), and choline (cho)	Neurochemistry biomarkers will be measured using single-voxel proton magnetic resonance spectroscopy (1H-MRS) in dorsolateral prefrontal cortex (DLPFC), primary somatosensory cortex (S1), anterior cingulate (ACC), insula and thalamus.	At baseline and post-intervention
Secondary	Neck pain intensity	The average intensity of neck pain will be assessed by using a 0-10 cm visual analogue scale (VAS), with 0 indicating no pain and 10 indicating worst imaginable pain.	At baseline and post-intervention
Secondary	Neck pain and disability	Neck Disability Index (NDI) will be used to assess how neck pain affects a patient's daily life and to assess the self-rated disability. A total score is 50, which a higher score indicates a higher disability.	At baseline and post-intervention
Secondary	Anxiety and depression	The symptoms of anxiety and depression will be assessed using Hospital Anxiety and Depression Scale (HADS). It includes two subscales: anxiety (HADS-A) and depression (HADS-D). A total score for each subscale ranges from 0 to 21, with higher scores indicating worse symptoms.	At baseline and post-intervention
Secondary	Cervical range of motion	Cervical range of motion (degrees) will be measured in flexion, extension, left-right lateral flexion and left-right rotation.	At baseline and post-intervention
Secondary	Cervical muscle strength	Cervical muscle strength will be measured in a craniocervical flexion action, using a handheld dynamometer (Newtons).	At baseline and post-intervention
Secondary	White matter integrity: fractional anisotropy (FA) and mean diffusivity (MD)	White matter in the brain will be quantified using diffusion tensor imaging (DTI) technique.	At baseline and post-intervention