Sub-acute Back PainPhase 4NCT01951105
Effect of L-dopa In Subacute Back Pain Population
A Phase 4 study testing Naproxen and Carbidopa/Levodopa in people with Sub-acute Back Pain, run by Northwestern University at 1 site in United States.
Trial summary
This study aims to determine if early treatment with Carbidopa/Levodopa and Naproxen in individuals with sub-acute back pain (SBP) is associated with changes in blocking transition to chronic back pain (CBP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sub-acute Back Pain
- What is being tested?
- Naproxen and Carbidopa/Levodopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2015to 25 Sep 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, over the age of 18 years, (no racial/ethnic restrictions)
- Must have a history of low back pain for a minimum of 4 weeks and a maximum of 12 weeks with signs and symptoms of radiculopathy: positive straight leg raising test with dermatomal radiation and/or myotomal weakness and/or reflex asymmetry; pain must radiate into buttock or below
- Must have a high risk phenotype for chronification of back pain (evaluated at baseline T1-MRI, DTI-MRI, and fMRI scans)
- Must have an average pain score over a 5 day period (average of ~15 measures on smartphone app) immediately preceding the baseline visit of ≥ 5 (on a 0-10 NRS) at the baseline visit
- Must be willing to read and able to understand instructions as well as PROs
- Must be in generally stable health Must sign an informed consent document after complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate
Who cannot join
- Previous (distinct) episodes of back pain onset (more than 3 distinct episodes of back pain lasting for a total of more than 4 weeks) in the previous year
- Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, chronic spinal stenosis, prior back surgery and history of tumor of the spine
- Low back pain associated with any systemic signs or symptoms, e.g., fever, chills
- Other comorbid chronic pain conditions such as fibromyalgia or neuropathic pain secondary to diabetes or post-herpes zoster
- Chronic neurologic conditions, including Parkinson's disease, Alzheimer's disease, and other conditions associated with dementia
- Significant other medical disease such as congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
Show all 35Show fewer
- Diabetes Type I or Type II
- History of glaucoma or narrow angle glaucoma
- Presence of undiagnosed skin lesions or history of melanoma
- Presence of severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease
- History of myocardial infarction with residual cardiac arrhythmia
- History of gastrointestinal bleeding or peptic ulcer
- Diagnosis of current depression (assessed via BDI, total > 28 are excluded) or psychiatric disorder requiring treatment, or such a diagnosis in the previous 6 months
- Use of therapeutic doses of antidepressant medications (i.e., tricyclic antidepressants, SSRIs, SNRIs; low doses used only in the evening for sleep will be allowed if dose is not changed)
- Current use of recreational drugs or recent history of alcohol abuse (pattern of drinking having social, financial or physical consequences) or drug abuse
- Any change in medication for back pain in the last 30 days
- High dose opioid prophylaxis, defined as > 50mg morphine equivalent/day
- Use of MAOIs, currently or within the past 2 weeks
- Prior use of Levodopa
- Use of any of the following drugs: bromocryptine, linezolid, metoclopramide, phenothiazines,promethazine/codeine, isoniazid, rifampin, pyrazinamide
- Oral iron supplementation
- Contraindications to use of study product, based on any of the following:
- Hypersensitivity to Carbidopa/Levodopa or other constituents of the Carbidopa/Levodopa capsules
- Hypersensitivity to lactose or other constituents of the placebo capsules
- Hypersensitivity to Naproxen or other constituents of the Naproxen capsules
- Hypersensitivity to Acetaminophen or other constituents of the Acetaminophen tablets
- Currently taking Levodopa or dopaminergic drugs
- Involvement in litigation regarding their back pain or having a disability claim or receiving workman's compensation or seeking either as a result of their low back pain
- In the judgment of the investigator, unable or unwilling to follow protocol and instructions
- Intra-axial implants (e.g. spinal cord stimulators or pumps)
- All exclusion criteria for MR safety: any metallic implants, pacemaker, brain or skull abnormalities, tattoos on large body parts, and claustrophobia
- Pregnancy or inability to use an effective method of birth control in sexually active men and women while taking the study drug and for one week thereafter. Barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUD's), hormonal contraceptives, oral contraceptive pills, surgical sterilization, and complete abstinence are examples of effective methods of contraception.
- Following laboratory abnormalities: liver function tests (SGOT/SGPT) greater than twice the upper limit of normal; unexplained anemia (Hgb <9 g/dL); evidence of renal insufficiency (creatinine >upper limit of normal) or any other abnormality that the principal investigator feels puts the subject at risk during the study
- History of chronic opioid use for pain management.
- Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
Official title: Corticostriatal Plasticity in the Transition to Chronic Pain: Effect of L-dopa
This study aims to determine if early treatment with Carbidopa/Levodopa and Naproxen in individuals with sub-acute back pain (SBP) is associated with changes in blocking transition to chronic back pain (CBP).
Read the detailed description
The transition from acute low back pain to chronic low back pain has been shown to be a result of changes in brain circuitry. Learning mechanisms give rise to the transition from acute to chronic pain and render the pain to become more emotional. The aim of this study is to further explore the idea that persistent pain, following an inciting injury, leads to an aversive learning signal that reorganizes the brain into a chronic pain state. We hypothesize that blocking the emotional/motivational learning response triggered by peripheral nerve injury in a critical time window will decrease the probability of transition to chronic pain. The primary hypothesis to be tested in the study is that early treatment with Carbidopa/Levodopa and Naproxen in individuals with sub-acute back pain (SBP) should decrease related reorganization and block transition to chronic back pain (CBP). This will be done through a 6 month, double-blind, randomized, placebo-controlled, three-arm, parallel-group trial of the pharmacological treatment Carbidopa/Levodopa for individuals (N = 200) with sub-acute back pain (SBP). A baseline MRI scan will be used to determine each subject's pain type and group assignment. Individuals with recovering sub-acute back pain will be observed over 6 months. Individuals with a persisting sub-acute back pain will be randomized to receive either 12 weeks of Carbidopa/Levodopa plus naproxen or placebo plus naproxen. The main outcome measurements will be the results of MRI scans at the baseline and final visit, assessment of back pain by the NRS pain scale, as well as pain assessment through self-reported questionnaires.
- Conditions
- Sub-acute Back Pain
- Being tested
- Naproxen, Carbidopa/Levodopa, Placebo
- Keywords
- Subacute, Back, Pain, Brain, MRI
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaproxenDrug
Also called Aleve, Anaprox, Antalgin, Apranax
Take one 250mg naproxen tablet three times a day for 12 weeks.
Carbidopa/LevodopaDrug
Also called Sinemet
12.5mg/50mg Carbidopa/Levodopa, administered orally as capsules, will be titrated up to TID over one week and then continued at that level for 4 weeks. If at the end of this initial 4 week period the participant has "responded," the subject will be maintained on that dose for the duration of the treatment period (12 weeks total). If there has not been a response, the dose will be increased to 25mg/100mg Carbidopa/Levodopa TID for the following 4 weeks at which time the pain status will be re-evaluated. If a response has occurred, that dose will be maintained in a blinded manner for the following 4 weeks of treatment; if not, further dose-titration will occur to 50mg/200mg Carbidopa/Levodopa TID for the final 4 weeks. If a subject experiences an AE at higher doses, then the subject will be given the next lower dose that s/he was able to tolerate and then be maintained on that dose for the remainder of the 12 week dosing period.
PlaceboDrug
Also called Sugar Pill
Take two placebo capsules three times a day for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Observation | No intervention | Individuals identified as having a recovering phenotype (SBPp) will be assigned to the observational arm and will be asked to continue his/her normal regime and return for the week 12 and week 24 visits for follow-up. |
| Carbidopa/Levodopa & Naproxen | Active comparator | Individuals identified as having a persisting phenotype (SBPr) will be treated with Carbidopa/Levodopa on a flexible dose-titration designed intervention based on dose-response TID throughout the 12 week treatment period.
Naproxen (250mg) capsules will be administered orally, one capsule TID, throughout the 12 week treatment period. Receives: Drug: Naproxen; Drug: Carbidopa/Levodopa |
| Placebo & Naproxen | Placebo comparator | Individuals identified as having a persisting phenotype (SBPr) will be treated with placebo capsule plus 250mg naproxen tablet three times a day for 12 weeks. Receives: Drug: Naproxen; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 20% Reduction in Pain on the NRS Pain Intensity Scale
Primary outcome is 20% reduction in pain intensity at p<0.1 based on pain ratings during 1 week prior to treatment and last week of study participation (at ~6months)
Measured: 6 months
Secondary outcomes (1)
Percent of Residual Pain Stratified by Gender for Individuals Receiving Treatment
Residual pain is computed based on pain ratings from the week prior to treatment and last week of study participation (at ~6months)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2013 (estimated)
- Study start24 Feb 2015
- Primary completion25 Sep 2017
- Study completion25 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sub-acute Back PainStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR)
- Responsible party
- Principal investigator, Apkar Apkarian, Northwestern University
- Investigators
- Apkar Apkarian, PhD, Principal investigator, Northwestern UniversityThomas J Schnitzer, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951105
- Sponsor's protocol ID
- STU00081444
- Other IDs
- R01DE022746
- Status last verified
- Mar 2021
- First submitted
- 17 Sep 2013
- Last updated
- 24 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Reckziegel D, Tetreault P, Ghantous M, Wakaizumi K, Petre B, Huang L, Jabakhanji R, Abdullah T, Vachon-Presseau E, Berger S, Baria A, Griffith JW, Baliki MN, Schnitzer TJ, Apkarian AV. Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial. Pain Ther. 2021 Dec;10(2):1375-1400. doi: 10.1007/s40122-021-00297-2. Epub 2021 Aug 10.
PubMed 34374961
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Corticostriatal Plasticity in the Transition to Chronic Pain: Effect of L-dopa
- ClinicalTrials.gov ID
- NCT01951105
- Acronym / sponsor ID
- STU00081444
- Conditions
- Sub-acute Back Pain
- Keywords
- Subacute, Back, Pain, Brain, MRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR)
- Study start
- 24 Feb 2015 (actual)
- Primary completion
- 25 Sep 2017 (actual)
- Study completion
- 25 Sep 2017 (actual)
- First posted
- 26 Sep 2013 (estimated)
- Results
- Posted 25 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to determine if early treatment with Carbidopa/Levodopa and Naproxen in individuals with sub-acute back pain (SBP) is associated with changes in blocking transition to chronic back pain (CBP).
Detailed description
The transition from acute low back pain to chronic low back pain has been shown to be a result of changes in brain circuitry. Learning mechanisms give rise to the transition from acute to chronic pain and render the pain to become more emotional. The aim of this study is to further explore the idea that persistent pain, following an inciting injury, leads to an aversive learning signal that reorganizes the brain into a chronic pain state. We hypothesize that blocking the emotional/motivational learning response triggered by peripheral nerve injury in a critical time window will decrease the probability of transition to chronic pain. The primary hypothesis to be tested in the study is that early treatment with Carbidopa/Levodopa and Naproxen in individuals with sub-acute back pain (SBP) should decrease related reorganization and block transition to chronic back pain (CBP). This will be done through a 6 month, double-blind, randomized, placebo-controlled, three-arm, parallel-group trial of the pharmacological treatment Carbidopa/Levodopa for individuals (N = 200) with sub-acute back pain (SBP). A baseline MRI scan will be used to determine each subject's pain type and group assignment. Individuals with recovering sub-acute back pain will be observed over 6 months. Individuals with a persisting sub-acute back pain will be randomized to receive either 12 weeks of Carbidopa/Levodopa plus naproxen or placebo plus naproxen. The main outcome measurements will be the results of MRI scans at the baseline and final visit, assessment of back pain by the NRS pain scale, as well as pain assessment through self-reported questionnaires.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Observation | No intervention | –Individuals identified as having a recovering phenotype (SBPp) will be assigned to the observational arm and will be asked to continue his/her normal regime and return for the week 12 and week 24 visits for follow-up. |
| Carbidopa/Levodopa & Naproxen | Active comparator | Drug: Naproxen, Drug: Carbidopa/LevodopaIndividuals identified as having a persisting phenotype (SBPr) will be treated with Carbidopa/Levodopa on a flexible dose-titration designed intervention based on dose-response TID throughout the 12 week treatment period. Naproxen (250mg) capsules will be administered orally, one capsule TID, throughout the 12 week treatment period. |
| Placebo & Naproxen | Placebo comparator | Drug: Naproxen, Drug: PlaceboIndividuals identified as having a persisting phenotype (SBPr) will be treated with placebo capsule plus 250mg naproxen tablet three times a day for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, over the age of 18 years, (no racial/ethnic restrictions)
- Must have a history of low back pain for a minimum of 4 weeks and a maximum of 12 weeks with signs and symptoms of radiculopathy: positive straight leg raising test with dermatomal radiation and/or myotomal weakness and/or reflex asymmetry; pain must radiate into buttock or below
- Must have a high risk phenotype for chronification of back pain (evaluated at baseline T1-MRI, DTI-MRI, and fMRI scans)
- Must have an average pain score over a 5 day period (average of ~15 measures on smartphone app) immediately preceding the baseline visit of ≥ 5 (on a 0-10 NRS) at the baseline visit
- Must be willing to read and able to understand instructions as well as PROs
Key exclusion criteria (35 listed)
- Previous (distinct) episodes of back pain onset (more than 3 distinct episodes of back pain lasting for a total of more than 4 weeks) in the previous year
- Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, chronic spinal stenosis, prior back surgery and history of tumor of the spine
- Low back pain associated with any systemic signs or symptoms, e.g., fever, chills
- Other comorbid chronic pain conditions such as fibromyalgia or neuropathic pain secondary to diabetes or post-herpes zoster
- Chronic neurologic conditions, including Parkinson's disease, Alzheimer's disease, and other conditions associated with dementia
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 |
|---|---|---|
| NaproxenAlso: Aleve, Anaprox, Antalgin, ApranaxTake one 250mg naproxen tablet three times a day for 12 weeks. | Drug | Carbidopa/Levodopa & Naproxen, Placebo & Naproxen |
| Carbidopa/LevodopaAlso: Sinemet12.5mg/50mg Carbidopa/Levodopa, administered orally as capsules, will be titrated up to TID over one week and then continued at that level for 4 weeks. If at the end of this initial 4 week period the participant has "responded," the subject will be maintained on that dose for the duration of the treatment period (12 weeks total). If there has not been a response, the dose will be increased to 25mg/100mg Carbidopa/Levodopa TID for the following 4 weeks at which time the pain status will be re-evaluated. If a response has occurred, that dose will be maintained in a blinded manner for the following 4 weeks of treatment; if not, further dose-titration will occur to 50mg/200mg Carbidopa/Levodopa TID for the final 4 weeks. If a subject experiences an AE at higher doses, then the subject will be given the next lower dose that s/he was able to tolerate and then be maintained on that dose for the remainder of the 12 week dosing period. | Drug | Carbidopa/Levodopa & Naproxen |
| PlaceboAlso: Sugar PillTake two placebo capsules three times a day for 12 weeks. | Drug | Placebo & Naproxen |
Primary outcome
Number of Participants With 20% Reduction in Pain on the NRS Pain Intensity Scale
Time frame: 6 months
Primary outcome is 20% reduction in pain intensity at p<0.1 based on pain ratings during 1 week prior to treatment and last week of study participation (at ~6months)
1 secondary outcome
Percent of Residual Pain Stratified by Gender for Individuals Receiving Treatment
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34374961Reckziegel D, Tetreault P, Ghantous M, Wakaizumi K, Petre B, Huang L, Jabakhanji R, Abdullah T, Vachon-Presseau E, Berger S, Baria A, Griffith JW, Baliki MN, Schnitzer TJ, Apkarian AV. Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial. Pain Ther. 2021 Dec;10(2):1375-1400. doi: 10.1007/s40122-021-00297-2. Epub 2021 Aug 10.
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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.
Apkar Apkarian, PhD principal investigator
Northwestern University
Thomas J Schnitzer principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naproxen and Carbidopa/Levodopa in people with Sub-acute Back Pain, run by Northwestern University at 1 site in United States.
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 6 inclusion and 35 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 24 Mar 2021. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With 20% Reduction in Pain on the NRS Pain Intensity Scale (time frame: 6 months). 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 NCT01951105, which also lists 1 linked publication.
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 24 Mar 2021.