Transition From Acute to Chronic Back Pain : Effect of L-dopa,Gender,and Associated Brain Plasticity

NCT ID: NCT04082715

Last Updated: 2020-01-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-31
• Study Completion Date: 2023-12-31

Brief Summary

This is a 6-month double-blinded, randomized, placebo-controlled clinical trial of pharmacological treatment (carbidopa/levodopa and celecoxib) for acute/subacute back pain. All eligible patients will be randomly assigned to 3 different group and receive a 12-week treatment of "carbidopa/levodopa+celecoxib ", of "placebo+celecoxib", and of "placebo+placebo". In addition, all participants will be MRI-scanned twice and assessed daily with a mobile app for pan, mood, and behavior.

Detailed Description

This is a 6-month double-blinded, randomized, placebo-controlled clinical trial of pharmacological treatment for acute/subacute back pain (carbidopa/levodopa and celecoxib).The dosage of carbidopa/levodopa is 25/100mg.After screening, all eligible patients will be randomly assigned to 3 different groups, with each receives a 12-week treatment of "carbidopa/levodopa+celecoxib (LDP+CLX)", of "placebo+celecoxib (PLC+CLX)", and of "placebo+placebo (PLC+PLC)". For each group, a subsequent 12-week follow-up efficacy evaluation will be conducted by telephone .At the end of the 24-week study, we will understand the durability of the treatment. During the drug treatment period for pain, all participants should return to the clinical follow-up center on week 0, 2, 6 and 12 to assess pain condition, properness of treatment and side effects .In the 24-week study of drug treatment and after treatment follow-up, pain and safety assessments will be conducted by telephone, at week 9, 16, and 20.In addition, all participants will be assessed daily with a mobile app for pain, mood and behavior.Participants will be scanned for brain structure images (T1), resting functional images (RS-fMRI) and diffusion tensor images (DTI) at the second follow-up visit (week 0) and at the end of study (week 24).

Conditions

Chronic Back Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

carbidopa/levodopa+celecoxib

carbidopa/levodopa+celecoxib treatments will be effective.

Group Type: EXPERIMENTAL

carbidopa/levodopa and celecoxib

Intervention Type: DRUG

Every patient of this arm will get one bottle of carbidopa/levodopa and one bottle of celecoxib. At treatment initiation, Carbidopa/Levodopa will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with carbidopa/levodopa twice daily for 3 days and then once daily for 3 days before discontinuing it completely.Celecoxib will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

placebo1+celecoxib

A placebo comparator for carbidopa/levodopa+celecoxib .

Group Type: PLACEBO_COMPARATOR

placebo1 and celecoxib

Intervention Type: DRUG

Every patient of this arm will get one bottle of placebo1 and one bottle of celecoxib. At treatment initiation, placebo1 will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with placebo1 twice daily for 3 days and then once daily for 3 days before discontinuing it completely. Celecoxib will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

placebo1+placebo2

A placebo comparator for carbidopa/levodopa+celecoxib and placebo1+celecoxib.

Group Type: PLACEBO_COMPARATOR

placebo1 and placebo2

Intervention Type: DRUG

Every patient of this arm will get one bottle of placebo1 and one bottle of placebo2. At treatment initiation, placebo1 will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with placebo1 twice daily for 3 days and then once daily for 3 days before discontinuing it completely. placebo2 will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

Interventions

carbidopa/levodopa and celecoxib

Every patient of this arm will get one bottle of carbidopa/levodopa and one bottle of celecoxib. At treatment initiation, Carbidopa/Levodopa will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with carbidopa/levodopa twice daily for 3 days and then once daily for 3 days before discontinuing it completely.Celecoxib will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

Intervention Type: DRUG

placebo1 and celecoxib

Every patient of this arm will get one bottle of placebo1 and one bottle of celecoxib. At treatment initiation, placebo1 will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with placebo1 twice daily for 3 days and then once daily for 3 days before discontinuing it completely. Celecoxib will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

Intervention Type: DRUG

placebo1 and placebo2

Every patient of this arm will get one bottle of placebo1 and one bottle of placebo2. At treatment initiation, placebo1 will be taken once daily for 3 days, then twice daily for 3 days, and then thrice daily over one week and then continue on that dose for the duration of the treatment period (12 weeks total). At the last treatment visit (end of the treatment period), patients will begin tapering off the medication as follows. S/he will start with placebo1 twice daily for 3 days and then once daily for 3 days before discontinuing it completely. placebo2 will remain constant once daily for patients of this arm throughout the treatment period, but it will not be given during the tapering down at the end of the treatment period(12 weeks total).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• New onset subacute or acute back pain (< 6 months' duration, no back pain for 3 months before the new onset)
• Signs and symptoms: positive straight leg raising test with dermatomal radiation and/or myotomal weakness and/or reflex asymmetry, pain must radiate into buttock or below
• Average reported pain intensity from App greater than 4/10 during the first week
• MUST be able to undergo MRI procedures (no pacemaker, any metal implants)

Exclusion Criteria

• 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 acute vertebral fracture;
• Low back pain associated with any systemic signs or symptoms, e.g., fever, chills;
• Symptoms of neuropathy due to diabetes Type I or Type II;
• Chronic neurologic conditions, including Parkinson's disease, Alzheimer's disease, and other conditions associated with dementia;
• Significant other medical diseases such as congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy;
• 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 (urine screening);
• Current use of cannabinoids (4 participants tested positive; 3 completed the study, in these blood test at the end of the study confirmed cannabinoid use; excluding these subjects does not importantly alter results, see below);
• 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;
• Currently taking levodopa or dopaminergic drugs
• In the judgment of the investigator, unable or unwilling to follow protocol and instructions
• 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 13.5 to 17.5 g/dL for men, 12.0 to 15.5g/dL for women); evidence of renal insufficiency (creatinine >upper limit of normal) or any other abnormality that the principal investigator feels puts the participant at risk during the study. A blood re-test could occur for all enrolled subjects within one month of the first blood draw due to potential risk for renal impairment with NSAIDs at this dosage;
• 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.
• 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 celecoxib capsules;
• Hypersensitivity to acetaminophen or other constituents of the acetaminophen tablets;
• Taking concomitant medication which may be adversely affected by omeprazole to a degree that alters subject's safety.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

BinBin Wu, doctor

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Wenzhou Medical University

Locations

Second Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Countries

China

Other Identifiers

SAHoWMU-CR2019-05-105

Identifier Type: -

Identifier Source: org_study_id