Knee OsteoarthritisNCT05570240
The Relationship Between Chronic OA Pain and Cognition Deficits in OA Patients.
An observational study of Knee Osteoarthritis and Neuroinflammatory Response, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
Trial summary
The goal of this observational study is to learn about the association between pain characteristics and cognitive functions in chronic knee osteoarthritis. The main questions it aims to answer are: 1. If pain characteristics affect cognitive functions in severe knee OA patients? 2. Read more about this study
- Who is it for?
- Ages 20 to 86 years
- Conditions the study is for
- Knee Osteoarthritis, Neuroinflammatory Response
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- 7 Aug 2019to 22 Apr 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 86 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: People with chronic knee osteoarthritis pain who will receive total knee replacement surgery. They have no other chronic pain except chronic knee pain. Furthermore they did not have any cerebral diseases such as stroke or brain tumor.
Who may be able to join
- OA patients who were scheduled to receive elective surgery which need spinal anesthesia.
- Age is more than 20 years old.
- American Society of Anesthesiologists (ASA) class I-III.
Who cannot join
- Unwilling to participate.
- Age is lesser than 20 years old.
- Autoimmune diseases.
- Previous knee injury or infection history.
- Brain region disease ex: stroke or brain tumor...etc.
- Mild cognitive impairment, dementia or other neurodegenerative diseases.
- Cancer.
- With other chronic pain.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Kaohsiung Veterans General Hopital
Kaohsiung City, Zuoying Dist, 813414
About this study
The goal of this observational study is to learn about the association between pain characteristics and cognitive functions in chronic knee osteoarthritis. The main questions it aims to answer are:
- If pain characteristics affect cognitive functions in severe knee OA patients?
- If concentration of neuroinflammation mediators were raised in severe knee OA patients with comparing with control group participants?
Participants will receive pain and cognition questionnaire before surgery and their blood and CSF will be collected for further analysis of neuroinflammation mediators.
Read the detailed description
In the previous studies, which revealed that because neural systems involved in cognition and pain processing are closely linked, they may affect with each other. In addition to sensory symptoms, cognitive functioning is thought to be affected in chronic pain patients. Pain uses cognitive resources, alters neural plasticity and affects expression and activity of a variety of chemical and cellular neuromediators. There are several brain regions such as amygdala and hippocampus which are most commonly activated during pain processing.Osteoarthritis (OA) of the knee is one of the leading causes of disability among noninstitutionalized elderly adults. One population-based study revealed that osteoarthritis increases the risk of cognitive deficits diseases such as dementia. However the possible mechanism had not be elucidated. Recent study revealed that OA-induced hyperalgesia was associated with increased nerve growth factor (NGF)/tropomycin receptor kinase A (TrkA) signaling. NGF activation of extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) may play a role in centralization of OA pain. Otherwise NGF has also been shown to produce a dramatic upregulation of brain-derived neurotrophic factor (BDNF) in trkA-expressing dorsal root ganglion (DRG) cells, and there is now growing evidence that BDNF may serve as a central regulator of excitability and is a neuromodulate or of central pain processing. On the other hand, in previous studies they showed that BDNF plays a critical role in synaptic plasticity, memory processes and storage of long-term memory. The BDNF/tropomycin receptor kinase B (TrkB) system in the hippocampus plays a crucial role not only in the memory acquisition, but also in the retention and / or recall of spatial memory.
Besides ongoing pain in chronic knee OA is characterized by increased brain activity in limbic-affective regions thus providing novel evidence for a strong emotional component of arthritis pain. There are feedback loops exist between pain, emotion and cognition. How is the role of BDNF in such loop? The objective of the study was the evaluation of association between pain characteristics and cognitive functions in severe knee OA patients. Besides, we will try to explore the possible mechanisms by which chronic OA like pain develops to cognitive deficits in animal models. The relationship between BDNF levels in body fluids (serum and CSF) and pain characteristics and cognitive function was also evaluated in the whole sample.
- Conditions
- Knee Osteoarthritis, Neuroinflammatory Response
- Keywords
- Chronic pain, Knee osteoarthritis, Cognitive deficits
- Medical subject headings
- Osteoarthritis, Knee, Chronic Pain, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| OA group | Knee osteoarthritis patients who were scheduled to receive elective total knee replacement surgery which need spinal anesthesia. | |
| Control group | Control group patients were scheduled to receive elective general surgery or urological surgery with spinal anesthesia. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Western Ontario and McMaster universities Osteoarthritis Index (WOMAC)
The WOMAC questionnaire has been used to assess subjects with OA of the hip or knee and consists of 24 items divided into 3 subscales: self-perception of pain (5 items), joint stiffness (2 items), and functional performance (17 items) during the previous 72 h.
Measured: The WOMAC questionnaire were measured on the day before their surgery.
The cognitive abilities screening instrument (CASI)
The CASI has been commonly used in dementia research and clinical practice to evaluate a subject's cognitive abilities.
Measured: The CASI questionnaire were measured on the day before their surgery.
Glia mediators of neuroinflammation
Glia mediators of neuroinflammation include interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF α), BDNF and fractalkine.
Measured: All blood and CSF samples were obtained before spinal anesthesia.
Secondary outcomes (1)
The geriatric depression scale (GDS-15)
The GDS-15 was used for evaluation of emotion especially for participant of age > 65. years old.
Measured: The GDS-15 questionnaire were measured on the day before their surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start7 Aug 2019
- Primary completion21 Apr 2021
- Study completion22 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaohsiung Veterans General Hospital.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chun-Hsien Wen, Kaohsiung Veterans General Hospital.
- Investigators
- Chun-Hsien Wen, Physician, Principal investigator, Kaohsiung Veterans General Hospital.Chen-Hsiu Chen, Physician, Study director, Kaohsiung Veterans General Hospital.Yuan-Yi Chia, Director, Study director, Kaohsiung Veterans General Hospital.Chih-Chi Tsai, RA, Study chair, Kaohsiung Veterans General Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05570240
- Sponsor's protocol ID
- VGHKS19-CT2-21
- Status last verified
- Oct 2022
- First submitted
- 4 Oct 2022
- Last updated
- 6 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j.cger.2010.03.001.
PubMed 20699159Kyrkanides S, Tallents RH, Miller JN, Olschowka ME, Johnson R, Yang M, Olschowka JA, Brouxhon SM, O'Banion MK. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice. J Neuroinflammation. 2011 Sep 7;8:112. doi: 10.1186/1742-2094-8-112.
PubMed 21899735Huang SW, Wang WT, Chou LC, Liao CD, Liou TH, Lin HW. Osteoarthritis increases the risk of dementia: a nationwide cohort study in Taiwan. Sci Rep. 2015 May 18;5:10145. doi: 10.1038/srep10145.
PubMed 25984812Li X, Tong Q, Gao J, Liu C; Alzheimer's Disease Neuroimaging Initiative; Liu Y. Osteoarthritis Was Associated With a Faster Decline in Hippocampal Volumes in Cognitively Normal Older People. Front Aging Neurosci. 2020 Aug 14;12:190. doi: 10.3389/fnagi.2020.00190. eCollection 2020.
PubMed 32922280Wu L, Wang X, Ye Y, Liu C. Association of Osteoarthritis With Changes in Structural Neuroimaging Markers Over Time Among Non-demented Older Adults. Front Aging Neurosci. 2021 Aug 10;13:664443. doi: 10.3389/fnagi.2021.664443. eCollection 2021.
PubMed 34447303Clark AK, Malcangio M. Fractalkine/CX3CR1 signaling during neuropathic pain. Front Cell Neurosci. 2014 May 7;8:121. doi: 10.3389/fncel.2014.00121. eCollection 2014.
PubMed 24847207Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014 Apr;14(4):217-31. doi: 10.1038/nri3621. Epub 2014 Feb 28.
PubMed 24577438Montague K, Malcangio M. The therapeutic potential of targeting chemokine signalling in the treatment of chronic pain. J Neurochem. 2017 May;141(4):520-531. doi: 10.1111/jnc.13927. Epub 2017 Feb 24.
PubMed 27973687Subbarayan MS, Joly-Amado A, Bickford PC, Nash KR. CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacol Ther. 2022 Mar;231:107989. doi: 10.1016/j.pharmthera.2021.107989. Epub 2021 Sep 4.
PubMed 34492237Cappoli N, Tabolacci E, Aceto P, Dello Russo C. The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception. J Neuroimmunol. 2020 Dec 15;349:577406. doi: 10.1016/j.jneuroim.2020.577406. Epub 2020 Sep 24.
PubMed 33002723Malfait AM, Miller RE, Block JA. Targeting neurotrophic factors: Novel approaches to musculoskeletal pain. Pharmacol Ther. 2020 Jul;211:107553. doi: 10.1016/j.pharmthera.2020.107553. Epub 2020 Apr 18.
PubMed 32311372Tang J, Bair M, Descalzi G. Reactive Astrocytes: Critical Players in the Development of Chronic Pain. Front Psychiatry. 2021 May 28;12:682056. doi: 10.3389/fpsyt.2021.682056. eCollection 2021.
PubMed 34122194
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Chronic OA Pain and Cognition Deficits in OA Patients.
- ClinicalTrials.gov ID
- NCT05570240
- Acronym / sponsor ID
- VGHKS19-CT2-21
- Conditions
- Knee Osteoarthritis, Neuroinflammatory Response
- Keywords
- Chronic pain, Knee osteoarthritis, Cognitive deficits
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Study start
- 7 Aug 2019 (actual)
- Primary completion
- 21 Apr 2021 (actual)
- Study completion
- 22 Apr 2021 (actual)
- First posted
- 6 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to learn about the association between pain characteristics and cognitive functions in chronic knee osteoarthritis. The main questions it aims to answer are:
- If pain characteristics affect cognitive functions in severe knee OA patients?
- If concentration of neuroinflammation mediators were raised in severe knee OA patients with comparing with control group participants?
Participants will receive pain and cognition questionnaire before surgery and their blood and CSF will be collected for further analysis of neuroinflammation mediators.
Detailed description
In the previous studies, which revealed that because neural systems involved in cognition and pain processing are closely linked, they may affect with each other. In addition to sensory symptoms, cognitive functioning is thought to be affected in chronic pain patients. Pain uses cognitive resources, alters neural plasticity and affects expression and activity of a variety of chemical and cellular neuromediators. There are several brain regions such as amygdala and hippocampus which are most commonly activated during pain processing.Osteoarthritis (OA) of the knee is one of the leading causes of disability among noninstitutionalized elderly adults. One population-based study revealed that osteoarthritis increases the risk of cognitive deficits diseases such as dementia. However the possible mechanism had not be elucidated. Recent study revealed that OA-induced hyperalgesia was associated with increased nerve growth factor (NGF)/tropomycin receptor kinase A (TrkA) signaling. NGF activation of extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) may play a role in centralization of OA pain. Otherwise NGF has also been shown to produce a dramatic upregulation of brain-derived neurotrophic factor (BDNF) in trkA-expressing dorsal root ganglion (DRG) cells, and there is now growing evidence that BDNF may serve as a central regulator of excitability and is a neuromodulate or of central pain processing. On the other hand, in previous studies they showed that BDNF plays a critical role in synaptic plasticity, memory processes and storage of long-term memory. The BDNF/tropomycin receptor kinase B (TrkB) system in the hippocampus plays a crucial role not only in the memory acquisition, but also in the retention and / or recall of spatial memory.
Besides ongoing pain in chronic knee OA is characterized by increased brain activity in limbic-affective regions thus providing novel evidence for a strong emotional component of arthritis pain. There are feedback loops exist between pain, emotion and cognition. How is the role of BDNF in such loop? The objective of the study was the evaluation of association between pain characteristics and cognitive functions in severe knee OA patients. Besides, we will try to explore the possible mechanisms by which chronic OA like pain develops to cognitive deficits in animal models. The relationship between BDNF levels in body fluids (serum and CSF) and pain characteristics and cognitive function was also evaluated in the whole sample.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OA group | – | –Knee osteoarthritis patients who were scheduled to receive elective total knee replacement surgery which need spinal anesthesia. |
| Control group | – | –Control group patients were scheduled to receive elective general surgery or urological surgery with spinal anesthesia. |
Who may qualify
- Ages
- 20 to 86 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- People with chronic knee osteoarthritis pain who will receive total knee replacement surgery. They have no other chronic pain except chronic knee pain. Furthermore they did not have any cerebral diseases such as stroke or brain tumor.
Key inclusion criteria (3 listed)
- OA patients who were scheduled to receive elective surgery which need spinal anesthesia.
- Age is more than 20 years old.
- American Society of Anesthesiologists (ASA) class I-III.
Key exclusion criteria (8 listed)
- Unwilling to participate.
- Age is lesser than 20 years old.
- Autoimmune diseases.
- Previous knee injury or infection history.
- Brain region disease ex: stroke or brain tumor...etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The Western Ontario and McMaster universities Osteoarthritis Index (WOMAC)
Time frame: The WOMAC questionnaire were measured on the day before their surgery.
The WOMAC questionnaire has been used to assess subjects with OA of the hip or knee and consists of 24 items divided into 3 subscales: self-perception of pain (5 items), joint stiffness (2 items), and functional performance (17 items) during the previous 72 h.
The cognitive abilities screening instrument (CASI)
Time frame: The CASI questionnaire were measured on the day before their surgery.
The CASI has been commonly used in dementia research and clinical practice to evaluate a subject's cognitive abilities.
Glia mediators of neuroinflammation
Time frame: All blood and CSF samples were obtained before spinal anesthesia.
Glia mediators of neuroinflammation include interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF α), BDNF and fractalkine.
1 secondary outcome
The geriatric depression scale (GDS-15)
Time frame: The GDS-15 questionnaire were measured on the day before their surgery.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
- Results publication: PubMed 20699159Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j.cger.2010.03.001.
- Results publication: PubMed 21899735Kyrkanides S, Tallents RH, Miller JN, Olschowka ME, Johnson R, Yang M, Olschowka JA, Brouxhon SM, O'Banion MK. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice. J Neuroinflammation. 2011 Sep 7;8:112. doi: 10.1186/1742-2094-8-112.
- Results publication: PubMed 25984812Huang SW, Wang WT, Chou LC, Liao CD, Liou TH, Lin HW. Osteoarthritis increases the risk of dementia: a nationwide cohort study in Taiwan. Sci Rep. 2015 May 18;5:10145. doi: 10.1038/srep10145.
- Results publication: PubMed 32922280Li X, Tong Q, Gao J, Liu C; Alzheimer's Disease Neuroimaging Initiative; Liu Y. Osteoarthritis Was Associated With a Faster Decline in Hippocampal Volumes in Cognitively Normal Older People. Front Aging Neurosci. 2020 Aug 14;12:190. doi: 10.3389/fnagi.2020.00190. eCollection 2020.
- Results publication: PubMed 34447303Wu L, Wang X, Ye Y, Liu C. Association of Osteoarthritis With Changes in Structural Neuroimaging Markers Over Time Among Non-demented Older Adults. Front Aging Neurosci. 2021 Aug 10;13:664443. doi: 10.3389/fnagi.2021.664443. eCollection 2021.
- Results publication: PubMed 24847207Clark AK, Malcangio M. Fractalkine/CX3CR1 signaling during neuropathic pain. Front Cell Neurosci. 2014 May 7;8:121. doi: 10.3389/fncel.2014.00121. eCollection 2014.
- Results publication: PubMed 24577438Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014 Apr;14(4):217-31. doi: 10.1038/nri3621. Epub 2014 Feb 28.
- Results publication: PubMed 27973687Montague K, Malcangio M. The therapeutic potential of targeting chemokine signalling in the treatment of chronic pain. J Neurochem. 2017 May;141(4):520-531. doi: 10.1111/jnc.13927. Epub 2017 Feb 24.
- Results publication: PubMed 34492237Subbarayan MS, Joly-Amado A, Bickford PC, Nash KR. CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacol Ther. 2022 Mar;231:107989. doi: 10.1016/j.pharmthera.2021.107989. Epub 2021 Sep 4.
- Results publication: PubMed 33002723Cappoli N, Tabolacci E, Aceto P, Dello Russo C. The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception. J Neuroimmunol. 2020 Dec 15;349:577406. doi: 10.1016/j.jneuroim.2020.577406. Epub 2020 Sep 24.
- Results publication: PubMed 32311372Malfait AM, Miller RE, Block JA. Targeting neurotrophic factors: Novel approaches to musculoskeletal pain. Pharmacol Ther. 2020 Jul;211:107553. doi: 10.1016/j.pharmthera.2020.107553. Epub 2020 Apr 18.
- Results publication: PubMed 34122194Tang J, Bair M, Descalzi G. Reactive Astrocytes: Critical Players in the Development of Chronic Pain. Front Psychiatry. 2021 May 28;12:682056. doi: 10.3389/fpsyt.2021.682056. eCollection 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chun-Hsien Wen, Physician principal investigator
Kaohsiung Veterans General Hospital.
Chen-Hsiu Chen, Physician study director
Kaohsiung Veterans General Hospital.
Yuan-Yi Chia, Director study director
Kaohsiung Veterans General Hospital.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Knee Osteoarthritis and Neuroinflammatory Response, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Western Ontario and McMaster universities Osteoarthritis Index (WOMAC) (time frame: The WOMAC questionnaire were measured on the day before their surgery.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05570240, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2022.