Whiplash InjuriesNCT01601912
Unraveling the Nature of Impaired Pain Inhibition in Patients With Chronic Whiplash-associated Disorders
An observational study of Whiplash Injuries, run by Vrije Universiteit Brussel at 1 site in Belgium.
Trial summary
The primary study aim is to unravel the nature of impaired pain inhibition during exercise in patients with chronic Whiplash-Associated Disorders (WAD). This will be ascertained by examining whether activation of serotonergic and/or noradrenergic descending pathways improves pain inhibition during exercise in these… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Whiplash Injuries
- What is being tested?
- Atomoxetine and Citalopram
- How many people
- 59 participants
- Where
- 1 siteBelgium
- Study dates
- Feb 2013to Dec 2013
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: WAD patients: primary care clinic \& community sample Healthy people: community sample
Who may be able to join
- WAD grades I to III according to the Quebec Task Force criteria
- experienced a whiplash trauma at least three months ago
- with chronic pain as a result of a whiplash injury
- 18-65 years of age and with Dutch as their native language will be able to participate
- 18-65 years of age and with Dutch as their native language will be able to participate
- having a sedentary job and doing < 3 h moderate physical activity/week
- being painfree without any chronic disease
Who cannot join
- other comorbidities or health issues that could explain the pain complaints
- < 18years > 65 years
- pregnant or until 1 year postnatal (for women)
- use of anti-depressive, anti-epileptic and pain medication.
- < 18years > 65 years
- pregnant or until 1 year postnatal (for women)
- use of anti-depressive, anti-epileptic and pain medication.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Universitair Ziekenhuis Brussel
Brussels, Brussels Capital, 1090
About this study
Official title: Unraveling the Nature of Impaired Pain Inhibition in Patients With Chronic Whiplash-associated Disorders: a Randomized Controlled Clinical Trial for the Treatment of Central Sensitization
The primary study aim is to unravel the nature of impaired pain inhibition during exercise in patients with chronic Whiplash-Associated Disorders (WAD). This will be ascertained by examining whether activation of serotonergic and/or noradrenergic descending pathways improves pain inhibition during exercise in these patients. In addition, it is aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways prevents post-exertional malaise following submaximal exercise in chronic WAD patients. A secondary study aim comprises of examining the effect of an acute submaximal exercise with and without activation of serotonergic or noradrenergic descending pathways on chronic WAD patients' cognitive performance. Furthermore, the isolated effect of activated serotonergic and noradrenergic descending pathways on chronic WAD patients' cognitive performance will be studied.
Read the detailed description
Chronic Whiplash-Associated Disorders (WAD) is a debilitating, costly condition, and remains a challenge for clinicians, including physicians, rehabilitation specialists and physiotherapists. There is now consistent evidence for central sensitization in people with chronic WAD. In a previous study in chronic WAD patients, our group showed that pain inhibition during exercise is impaired and that a submaximal exercise triggers a severe relapse named post-exertional malaise. On the other hand, imbalance of serotonin (5-HT) and norepinephrine (NE) is likely to be responsible for malfunctioning of pain inhibitory pathways. Indeed, NE is required for activation of descending noradrenergic pathways with established nociceptive inhibitory properties. Serotonin reuptake inhibitor drugs activate serotonergic descending pathways that recruit, in part, opioid peptide-containing interneurons in the dorsal horn. It becomes more and more clear that the lack of pain inhibition accounts in part for various symptoms at rest and following exercise in particular (post-exertional malaise). However, the mechanisms behind the lack of pain inhibition during exercise remain to be revealed. Besides the lack of endogenous pain inhibition during exercise in people with chronic WAD, there appears to be sufficient evidence to support the presence of impaired cognitive function in chronic pain patients in general and preliminary evidence in chronic WAD patients in particular.
The present study aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways improves pain inhibition during exercise in chronic WAD patients. In addition, it is aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways prevents post-exertional malaise following submaximal exercise in these patients. A secondary study aim comprises of examining the effect of an acute submaximal exercise with and without activation of serotonergic or noradrenergic descending pathways on chronic WAD patients' cognitive performance. Furthermore, the isolated effect of activated serotonergic and noradrenergic descending pathways on chronic WAD patients' cognitive performance will be studied.We will modulate endogenous serotonergic and adrenergic pain inhibitory mechanisms by using a selective NE reuptake inhibitor (NRI) and a selective 5-HT reuptake inhibitor (SSRI). Endogenous pain inhibition and cognitive function (sustained and selective attention, and executive function) will be studied at rest and in response to exercise (1) under baseline condition, (2) after the intake of a NRI (Atomoxetine), and (3) after the intake of a SSRI (Citalopram).
- Conditions
- Whiplash Injuries
- Being tested
- Atomoxetine, Citalopram
- Keywords
- Whiplash Injuries, Chronic Pain, Exercise, Cognition
- Medical subject headings
- Whiplash Injuries, Chronic Pain, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtomoxetineDrug
Also called Strattera (Eli Lilly Nederland B.V)
40 mg, 1 application
CitalopramDrug
Also called Citalopram Sandoz (Sandoz N.V.)
20 mg, 1 application
| Study group | Role | What they receive |
|---|---|---|
| Atomoxetine NRI | We will modulate endogenous adrenergic pain inhibitory mechanisms by using a selective norepinephrine reuptake inhibitor (NRI). Receives: Drug: Atomoxetine | |
| Citalopram SSRI | We will modulate serotonergic pain inhibitory mechanisms by using a selective serotonin reuptake inhibitor (SSRI) Receives: Drug: Citalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in pain inhibition
To investigate pain inhibition, a combination of temporal en spatial summation will be used on the example of Cathcart et al. (2009). Temporal summation is applied by using an analogue Wagner pressure algometer and spatial summation is induced by causing ischemic pain with an inflatable cuff.
Measured: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
Changes in psychomotor vigilance and alertness
To investigate cognitive function we used the Psychomotor Vigilance Task (PVT) which is a 10-minute test.
Measured: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
Changes in selective attention and executive function
The Stroop task is used to assess selective attention and executive function
Measured: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
Secondary outcomes (3)
Change in scores on the Neck Disability Index questionnaire
The NDI was developed as a modification of the Oswestry Back Pain Index and was the first instrument designed to assess self-rated disability in patients with neck pain. The NDI is a valid and reliable instrument, sensitive to measure changes within a population of patients with neck pain.
Measured: Baseline = day 1, after the first intervention = day 8, after the second intervention = day 15
Change in scores on the Brief Pain Inventory questionnaire
The BPI - short form includes 8 questions about one's pain levels and location in the body, and 7 questions about the daily interferences due to pain and it is sensitive to brief therapeutic interventions.
Measured: Baseline = day 1, after the first intervention = day 8, after the second intervention = day 15
Changes in the scores on the Whiplash Associated Disorders Symptom list
This is a self-reported measure for assessing symptom severity in patients with WAD. The questionnaire is composed of the most reported WAD symptoms in the literature and some autonomic symptoms. Every symptom is presented by a visual analog scale (VAS) (100 mm), a method that is known for its validity and reliability.
Measured: Day 1 pre and post submaximal graded exercise and 24h after exercise = day 1 A,B&C, day 8 pre and post submaximal graded exercise & 24h after exercise = day 8 A,B&C, day 15 pre and post submaximal graded exercise & 24h after exercise = day 15 A,B&C
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2012 (estimated)
- Study startFeb 2013
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Whiplash InjuriesStudies of the same condition, open and under way.
- More trials run by Vrije Universiteit BrusselThe sponsor's other registered studies.
- 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
- Cross-sectional
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vrije Universiteit Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kelly Ickmans, Vrije Universiteit Brussel
- Investigators
- Jo Nijs, PhD, Study director, Vrije Universiteit Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01601912
- Sponsor's protocol ID
- WFWG-22
- Status last verified
- Jan 2014
- First submitted
- 14 May 2012
- Last updated
- 14 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Van Oosterwijck J, Nijs J, Meeus M, Van Loo M, Paul L. Lack of endogenous pain inhibition during exercise in people with chronic whiplash associated disorders: an experimental study. J Pain. 2012 Mar;13(3):242-54. doi: 10.1016/j.jpain.2011.11.006. Epub 2012 Jan 24.
PubMed 22277322Ickmans K, Malfliet A, De Kooning M, Goudman L, Hubloue I, Schmitz T, Goubert D, Aguilar-Ferrandiz ME. Lack of Gender and Age Differences in Pain Measurements Following Exercise in People with Chronic Whiplash-Associated Disorders. Pain Physician. 2017 Sep;20(6):E829-E840.
PubMed 28934789
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unraveling the Nature of Impaired Pain Inhibition in Patients With Chronic Whiplash-associated Disorders: a Randomized Controlled Clinical Trial for the Treatment of Central Sensitization
- ClinicalTrials.gov ID
- NCT01601912
- Acronym / sponsor ID
- WFWG-22
- Conditions
- Whiplash Injuries
- Keywords
- Whiplash Injuries, Chronic Pain, Exercise, Cognition
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Vrije Universiteit BrusselUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 18 May 2012 (estimated)
- 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 primary study aim is to unravel the nature of impaired pain inhibition during exercise in patients with chronic Whiplash-Associated Disorders (WAD). This will be ascertained by examining whether activation of serotonergic and/or noradrenergic descending pathways improves pain inhibition during exercise in these patients. In addition, it is aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways prevents post-exertional malaise following submaximal exercise in chronic WAD patients. A secondary study aim comprises of examining the effect of an acute submaximal exercise with and without activation of serotonergic or noradrenergic descending pathways on chronic WAD patients' cognitive performance. Furthermore, the isolated effect of activated serotonergic and noradrenergic descending pathways on chronic WAD patients' cognitive performance will be studied.
Detailed description
Chronic Whiplash-Associated Disorders (WAD) is a debilitating, costly condition, and remains a challenge for clinicians, including physicians, rehabilitation specialists and physiotherapists. There is now consistent evidence for central sensitization in people with chronic WAD. In a previous study in chronic WAD patients, our group showed that pain inhibition during exercise is impaired and that a submaximal exercise triggers a severe relapse named post-exertional malaise. On the other hand, imbalance of serotonin (5-HT) and norepinephrine (NE) is likely to be responsible for malfunctioning of pain inhibitory pathways. Indeed, NE is required for activation of descending noradrenergic pathways with established nociceptive inhibitory properties. Serotonin reuptake inhibitor drugs activate serotonergic descending pathways that recruit, in part, opioid peptide-containing interneurons in the dorsal horn. It becomes more and more clear that the lack of pain inhibition accounts in part for various symptoms at rest and following exercise in particular (post-exertional malaise). However, the mechanisms behind the lack of pain inhibition during exercise remain to be revealed. Besides the lack of endogenous pain inhibition during exercise in people with chronic WAD, there appears to be sufficient evidence to support the presence of impaired cognitive function in chronic pain patients in general and preliminary evidence in chronic WAD patients in particular.
The present study aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways improves pain inhibition during exercise in chronic WAD patients. In addition, it is aimed at examining whether activation of serotonergic and/or noradrenergic descending pathways prevents post-exertional malaise following submaximal exercise in these patients. A secondary study aim comprises of examining the effect of an acute submaximal exercise with and without activation of serotonergic or noradrenergic descending pathways on chronic WAD patients' cognitive performance. Furthermore, the isolated effect of activated serotonergic and noradrenergic descending pathways on chronic WAD patients' cognitive performance will be studied.We will modulate endogenous serotonergic and adrenergic pain inhibitory mechanisms by using a selective NE reuptake inhibitor (NRI) and a selective 5-HT reuptake inhibitor (SSRI). Endogenous pain inhibition and cognitive function (sustained and selective attention, and executive function) will be studied at rest and in response to exercise (1) under baseline condition, (2) after the intake of a NRI (Atomoxetine), and (3) after the intake of a SSRI (Citalopram).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atomoxetine NRI | – | Drug: AtomoxetineWe will modulate endogenous adrenergic pain inhibitory mechanisms by using a selective norepinephrine reuptake inhibitor (NRI). |
| Citalopram SSRI | – | Drug: CitalopramWe will modulate serotonergic pain inhibitory mechanisms by using a selective serotonin reuptake inhibitor (SSRI) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- WAD patients: primary care clinic \& community sample Healthy people: community sample
Key inclusion criteria (7 listed)
- WAD grades I to III according to the Quebec Task Force criteria
- experienced a whiplash trauma at least three months ago
- with chronic pain as a result of a whiplash injury
- 18-65 years of age and with Dutch as their native language will be able to participate
- 18-65 years of age and with Dutch as their native language will be able to participate
Key exclusion criteria (7 listed)
- other comorbidities or health issues that could explain the pain complaints
- < 18years > 65 years
- pregnant or until 1 year postnatal (for women)
- use of anti-depressive, anti-epileptic and pain medication.
- < 18years > 65 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtomoxetineAlso: Strattera (Eli Lilly Nederland B.V)40 mg, 1 application | Drug | Atomoxetine NRI |
| CitalopramAlso: Citalopram Sandoz (Sandoz N.V.)20 mg, 1 application | Drug | Citalopram SSRI |
Primary outcome
Changes in pain inhibition
Time frame: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
To investigate pain inhibition, a combination of temporal en spatial summation will be used on the example of Cathcart et al. (2009). Temporal summation is applied by using an analogue Wagner pressure algometer and spatial summation is induced by causing ischemic pain with an inflatable cuff.
Changes in psychomotor vigilance and alertness
Time frame: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
To investigate cognitive function we used the Psychomotor Vigilance Task (PVT) which is a 10-minute test.
Changes in selective attention and executive function
Time frame: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B
The Stroop task is used to assess selective attention and executive function
3 secondary outcomes
Change in scores on the Neck Disability Index questionnaire
Time frame: Baseline = day 1, after the first intervention = day 8, after the second intervention = day 15
Change in scores on the Brief Pain Inventory questionnaire
Time frame: Baseline = day 1, after the first intervention = day 8, after the second intervention = day 15
Changes in the scores on the Whiplash Associated Disorders Symptom list
Time frame: Day 1 pre and post submaximal graded exercise and 24h after exercise = day 1 A,B&C, day 8 pre and post submaximal graded exercise & 24h after exercise = day 8 A,B&C, day 15 pre and post submaximal graded exercise & 24h after exercise = day 15 A,B&C
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 14 Jan 2014.
- Background: PubMed 22277322Van Oosterwijck J, Nijs J, Meeus M, Van Loo M, Paul L. Lack of endogenous pain inhibition during exercise in people with chronic whiplash associated disorders: an experimental study. J Pain. 2012 Mar;13(3):242-54. doi: 10.1016/j.jpain.2011.11.006. Epub 2012 Jan 24.
- Derived from this study: PubMed 28934789Ickmans K, Malfliet A, De Kooning M, Goudman L, Hubloue I, Schmitz T, Goubert D, Aguilar-Ferrandiz ME. Lack of Gender and Age Differences in Pain Measurements Following Exercise in People with Chronic Whiplash-Associated Disorders. Pain Physician. 2017 Sep;20(6):E829-E840.
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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.
Jo Nijs, PhD study director
Vrije Universiteit Brussel
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 Whiplash Injuries, run by Vrije Universiteit Brussel at 1 site in Belgium.
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 7 inclusion and 7 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 14 Jan 2014. 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 Belgium. 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?
Changes in pain inhibition (time frame: Baseline before and after the submaximal graded exercise= day 1 A & B, after first intervention before and after the submaximal graded exercise= day 8 A & B, after second intervention before and after the submaximal graded exercise = day 15 A & B). 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 NCT01601912, which also lists 2 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 14 Jan 2014.