Genetic Variants Associated With Low Back Pain and Their Response to Treatment With Duloxetine or Propranolol

• Status: Terminated
• Trial end date: 2018-05-31
• Target enrollment: 0
• Participant gender: All

Summary

This study is a randomized, double-blind, placebo controlled, three period crossover clinical trial. The main purpose of this study is to determine if Chronic Low Back Pain patients presenting with either localized or widespread painful symptoms respond differently to treatment with Duloxetine or Propranolol, and if the effectiveness of treatment with these drugs can determined by the presence or absence of SNPs associated with the Serotonin receptor or Cathecol-O-MethylTransferase activity. Each treatment period will be of two weeks duration with a 1 week washout phase between treatment periods. Following a Latin square design, patients will be randomly assigned to one of six different treatment groups, starting their first treatment cycle with either Duloxetine, Propranolol or Placebo and rotating through the other treatments in the subsequent cycles. Effectiveness of treatment will be measured by means of Pain Index as the primary outcome measure, and secondary outcome measures will include Pressure Pain Threshold and the Pain Disability Index, Perceived Stress Scale, Symptom Checklist -90R and the Patient's Global Impression of Change questionnaires.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mark Ware
• Treatments: Duloxetine Hydrochloride; Propranolol; Serotonin

Criteria

1. Male or Female patients aged 18 or above.

2. Chronic Low Back Pain as the primary painful condition. CLBP diagnose based on medical history and physical examination, with pain restricted to the low back (T6 or below), with or without radiation to the lower limbs but no neurologic signs defined as per the Quebec Task Force on Spinal Disorders Class 1 to 3. This pain must be persistent in the lower back ≥4 days/week for the past 6 months or longer.

3. Average pain score of ≥4 at the time of recruitment.

4. Women of childbearing potential must agree not to become pregnant during the time of the study and to use adequate contraception during this time. Adequate contraception will be defined as the use of highly effective or double barrier methods. When used consistently and correctly, "double barrier" methods of contraception (e.g. male condom with diaphragm, male condom with cervical cap) can be used as an effective alternative to the highly effective contraception methods such as combined oral contraceptives, injectables or intrauterine devices. Both options will be discussed during the informed consent process.

5. Stable drug regimen for 1 month prior to entering the study and throughout the study. Patients will not be taken off their current pain medication to participate in the study, but they will be asked to keep a stable regimen (not change any doses, add or remove other medication) during the study.

6. Ability to follow study protocol (cognitive and situational).

7. Ability to write and speak in English and/or French.

8. Agrees to provide signed and dated informed consent form and biobanking consent form.

9. Willing to comply with all study procedures, including the biobanking aspect of the project and to be available for the duration of the study.

Exclusion Criteria:

1. Uncontrolled medical or psychiatric conditions.

2. History of major depressive disorder, psychotic disorder or schizophrenia, and/or manic episodes within the past year.

3. Pregnancy and/or breast-feeding. Patients who are unsure of their status will also be excluded from participating

4. Pain due to cancer.

5. Disability compensation or litigation.

6. Neurologic signs of lumbosacral radiculopathy within the past 6 months: lower extremity muscle weakness/sensory loss in a dermatomal distribution, abnormal deep tendon reflexes.

7. Radiographic and/or electrophysiology evidence of radicular compression in the past 6 months.

8. Clinical signs of lumbar stenosis within the past 6 months: numbness, weakness, and/or discomfort radiating from the spine down to the buttocks and legs while walking or in prolonged standing and relieved with sitting or lying.

9. Clinical signs of back pain that requires an urgent/alternative intervention: new onset bowel/bladder incontinence, saddle anaesthesia, foot drop, unexplained weight loss, fever.

10. Radiographic evidence of spinal stenosis, high-grade spondylolisthesis (grade 3 or 4), acute spinal fracture, tumour, abscess or acute pathology in the low back/abdominal area in the past 6 months.

11. Low back surgery (lumbosacral spine) within the past 12 months, or history of more than 1 low back surgery.

12. Minimally invasive procedures aimed to reduce pain in the lumbosacral area within the past month (Medial Branch Blocks/Ablations, Epidural Steroid Injections, Trigger point injections, Sacroiliac Joint Injections, Greater Trochanteric/Acetabulofemoral Joint Injections).

13. Known hypersensitivity to Beta Blockers or SNRIs.

14. Currently taking SNRIs, Beta Blockers, Opioids at a daily dose superior to 30mg of Morphine Oral Equivalent, Tricyclic Antidepressants, Methylene Blue, Linezolid, Monoamine Oxidase Inhibitors (such as Selegiline, Isoniazid, Procarbazine), Thioridazine, CYP1A2 inhibitors (Fluvoxamine, Verapamil, Cimetidine, Fluoroquinolone antibiotics such as Ciprofloxacin).

15. Active alcoholism within the past 6 months.

16. Psychoactive recreational drug abuse within the past 6 months including MDMA, Ketamine, hallucinogens such as LSD and/or sympathomimetics such as Cocaine.

17. Patients with asthma, cardiac arrhythmias such as Wolff-Parkinson-White syndrome, coronary artery disease, congestive heart failure, renal failure or dialysis, liver insufficiency, diabetes mellitus, hyperthyroidism.

18. Heart rate less than 60 bpm or systolic/diastolic blood pressure less than 105/60 mmHg during the initial visit.