Studying the Neurobiological Mechanisms of Non-specific Chronic Low Back Pain and Chronic Insomnia: a Four-group Cross-sectional Study

NCT06973837 | Recruiting DMC

• 3 other identifiers: 11PMF24NG080423NS68780
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a part of a larger project aiming to evaluate the neurobiological mechanisms underlying the relationship between sleep and pain in people with non-specific chronic low back pain. Specifically, this study aims to evaluate the neurobiological mechanisms underlying the relationship between chronic sleep disturbances and pain sensitivity in people with non-specific chronic low back pain and chronic insomnia.

Conditions

Chronic Low Back Pain (CLBP); Chronic Insomnia; Neuroinflammation

Keywords

Pain; Chronic pain; Chronic low back pain; Sleep; Insomnia; Chronic insomnia; Magnetic resonance imaging; Functional magnetic resonance imaging; Magnetic resonance spectroscopy; Diffusion weighted imaging; Quantitative sensory testing; Temporal summation; Conditioned pain modulation; Experience sampling method; Ecological momentary assessment; Microbiota; Gut-Brain axis; Short-chain fatty acids

Outcome Measures

Primary Outcomes (1)

• Brain metabolite concentrations

  Concentration of brain metabolites measured using single-voxel magnetic resonance spectroscopy in five regions of interest: (1) pregenual anterior cingulate cortex (midline); (2/3) right/left thalamus; (4/5) right/left anterior insula.

  Day 2

Secondary Outcomes (20)

• Brain-tissue microstructure diffusivity

  Day 2

• Functional brain responses to evoked low back pain

  Day 2

• Manual pressure pain detection thresholds (mPDT)

  Day 1

• Computerized pressure pain detection thresholds (cPDT)

  Day 1

• Computerized pressure pain tolerance thresholds (cPTT)

  Day 1

Other Outcomes (18)

• Pre-scanning total sleep time

  One night between Day 1 and 2

• Pre-scanning sleep efficiency

  One night between Day 1 and 2

• Self-reported (REDCap) mood state assessed via a short (32-item) version of the Profile of Mood States (POMS-32)

  Day 2

Study Arms (4)

Pain-free with good sleep habits (healthy controls)

Meeting all General inclusion/exclusion criteria and Pharmacological exceptions criteria, plus the specific inclusion criteria for "pain-free" and "good sleeper".

Other: Real-life monitoring, experimental pain testing, brain imaging, blood and stool sampling.

Non-specific chronic low back pain with good sleep habits

Meeting all General inclusion/exclusion criteria and Pharmacological exceptions criteria, plus the specific inclusion criteria for "chronic low back pain" and "good sleeper".

Other: Real-life monitoring, experimental pain testing, brain imaging, blood and stool sampling.

Pain-free with chronic insomnia

Meeting General inclusion/exclusion criteria and Pharmacological exceptions criteria, plus the specific inclusion criteria for "pain-free" and "chronic insomnia".

Other: Real-life monitoring, experimental pain testing, brain imaging, blood and stool sampling.

Non-specific chronic low back pain with comorbid chronic insomnia

Meeting all General inclusion/exclusion criteria and Pharmacological exceptions criteria, plus the specific inclusion criteria for "chronic low back pain" and "chronic insomnia".

Other: Real-life monitoring, experimental pain testing, brain imaging, blood and stool sampling.

Interventions

Real-life monitoring, experimental pain testing, brain imaging, blood and stool sampling. OTHER

See detailed study description and outcome measures.

Non-specific chronic low back pain with comorbid chronic insomnia; Non-specific chronic low back pain with good sleep habits; Pain-free with chronic insomnia; Pain-free with good sleep habits (healthy controls)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants across all study groups will be recruited from the broad area around Leuven, Belgium, via local flyers and social media. Participants with non-specific chronic low back pain and/or chronic insomnia will also be recruited from the pain and/or sleep center of UZ Leuven, Belgium, as well as via primary care units and patient support groups targeting people in the Leuven area. Participants will be recruited and stratified according to sex and age to enable matching to the primary group of interest (chronic low back pain and comorbid insomnia), and a majority of females (\~two thirds) will be recruited to better represent the sex-distribution within the population representative of this group.

You may qualify if:

• years old.
• Ability to speak and understand the Dutch Language.
• Body mass index \<30.
• No smoking or nicotine use.
• Low caffeine use (≤3 cups of coffee/day, ≤1 energy drink/day).
• Low alcohol use (≤9 alcoholic units/week).
• No use of neuro- and/or psychopharmacological treatments and/or immunosuppressive agents (including NSAIDs) with a suspected influence on neuroinflammation unless terminated within a sufficient time frame before the start of the study, or unless falling under the Pharmacological exceptions criteria (see below).
• Willing to (try to) adhere to the acute pre-test restrictions, including refraining from analgesics (unless stable use), caffeine, alcohol, and/or strenuous physical activity (\>3 METs) in the 24 hours preceding the main test day.

You may not qualify if:

• Shift worker.
• Use of blood thinners.
• (History of) Substance dependence/abuse.
• Chronic pain conditions (≥3 months) other than chronic low back pain.
• Severe intrinsic sleep disorders (assessed during a one-night, laboratory-based polysomnography).
• Restless leg syndrome
• Central or peripheral neurological disorder/condition (e.g., epilepsy, multiple sclerosis, peripheral neuropathy).
• History of spinal surgery.
• Major medical (e.g., cardiac disease, cancer) and/or psychiatric disorder/disease (e.g., major depressive disorder, bipolar disorder).
• Claustrophobia.
• Contraindications for magnetic resonance imaging (e.g., metal/cochlear implants, pacemaker).
• Pregnancy or being \<12 months post-natal.
• Pharmacological exceptions criteria:
• \- Participants with chronic low back pain and/or (comorbid) insomnia will be allowed to be on a stable low dose of weak pain and/or sleep agents (e.g., Tramadol, Zolpidem) if medically prescribed specifically for their low back pain and/or insomnia, and if approved by the national medicine register of Belgium (FAMHP, Federal Agency for Medicine and Health Products). These participants will also be allowed stable and/or occasional use of low-to-moderate doses of over-the-counter medications for pain and/or sleep that are suspected to have no or minimal impact on neuroinflammation (e.g., paracetamol, melatonin). Habitual use of medications according to the above-stated criteria should be maintained across the entire study period, with the only exception being analgesics taken on an occasional basis. Specifically, because of the extensive battery of pain tests that will be utilized in the study, all analgesics that are only taken occasionally should be refrained from during the 24 hours preceding the main test day (pre-test instructions).
• Currently pain free, defined as having no pain that affects daily living/functioning and/or which has led to a consultation with a healthcare practitioner.

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead
• Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek): collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (1)

UZ/KU Leuven

Leuven, 3000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Systemic venous blood samples will be taken, from which designated serum will be extracted for the analysis of short chain fatty acids and highly-sensitive C-reactive protein.

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Neuroinflammatory Diseases; Pain; Chronic Pain

Interventions

Neuroimaging; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative

Central Study Contacts

Iris Coppieters, PT, PhD

CONTACT

+32 497 92 90 32; iris.coppieters@vub.be

Elin Johansson, PT, MSc

CONTACT

+46 702 05 54 52; elinmarie.johansson@kuleuven.be

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Iris Coppieters (Principal investigator)

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 15, 2025
• Study Start: October 3, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The data will become available upon publication with no time limitations.
• Access Criteria: The data will be publicly available.

Locations

BE (1)