Effects of Metformin on Low Back Pain

Study Overview
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Brief Summary
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The purpose of the current study is to determine the effects of metformin in non-diabetic patients with low back pain, and identify novel targets for future treatments

Official Title
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Metformin and Beyond: Individualizing Care for Low Back Pain

Conditions
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Low Back Pain

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 and above Diagnosed with axial low back pain (low back pain more severe than pain in other parts of the body, without radiation of pain into the lower extremities). Women of child bearing potential must have a negative serum pregnancy test at baseline. Exclusion Criteria: Diagnosed with rheumatoid arthritis, lupus, other autoimmune/systemic inflammatory arthropathies Progressive lower extremity weakness or numbness Recent oral steroid use (within last 3 months) NSAID use Chronic kidney disease (eGFR <60) Diagnosis of diabetes mellitus Subjects must not be pregnant or breastfeeding, or planning to become pregnant or breastfeed during the course of the trial Unable to take an oral medication in a non crushable pill form Taking metformin presently or within the last 6 months History of allergy to metformin History of lactic acidosis Severe Hepatic dysfunction Currently taking a diabetic medication such as sitagliptin, saxagliptin, linagliptin, alogliptin, sitagliptin with metformin Currently taking a Carbonic anhydrase inhibitor such as topiramate, zonisamide, acetazolamide, dichlorphenamide, methazolamide Currently taking cimetidine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Metformin<br>High Dose Metformin Group (n=100). Subjects will receive metformin and will be instructed to take 2 tabs per day (1,000mg) for the first week then increase to 3 tabs per day (1,500mg) for the remaining 6 months. | Drug: Metformin<br>* 500mg tabs of Metformin Extended Release<br>* Other names: Metformin ER;|
| Experimental: Low Dose Metformin<br>Low Dose Metformin Group (n=100). Subjects will receive metformin and will be instructed to take 1 tab per day (1 metformin tab (500mg) for 6 months. | Drug: Metformin<br>* 500mg tabs of Metformin Extended Release<br>* Other names: Metformin ER;|
| Placebo Comparator: Placebo<br>Placebo Group (n=100). Subjects will receive placebo and will be instructed to take either 2 tabs per day for the first week then increase to 3 tabs per day for the remaining 6 months OR take 1 placebo tab for 6 months. | Drug: Placebo<br>* Placebo Tabs<br>|
| Other: Wait-List Control<br>Control Group (n=100). Subjects will be told that they are in the wait-list control group. They will have a 3 month waiting period before they will be randomized again to a treatment group. They will be randomized to one of the previous groups. | Drug: Metformin<br>* 500mg tabs of Metformin Extended Release<br>* Other names: Metformin ER;Drug: Placebo<br>* Placebo Tabs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Numeric Pain Rating Scale | Scores range from 0 to 10 with a higher score indicating more severe pain | Up to 15 months | 
| Change from baseline in Oswestry Disability Index | Scores range from 0% to 100% with higher percentage scores indicating greater disability | Up to 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Connor-Davidson Resilience Scale 25 | Scores range from 0 to 100 in which a higher score demonstrates greater resilience | Up to 15 months | 
| Change from baseline in 10 Meter Walk Test | Subject is timed walking at normal speed and also fastest speed possible. A faster time is associated with better outcome. | Up to 15 months | 
| Change from baseline in Fear Avoidance Questionnaire | Scores range from 0 to 96 in which a higher score indicates greater fear avoidance beliefs | Up to 15 months | 
| Change from baseline in Godin Leisure Time Questionnaire | Minimum score is 0 and there is no maximum score. A higher score indicates a more active individual. | Up to 15 months | 
| Change from baseline in Catastrophizing Scale | Score range from 0 to 36 with a higher score indicating a higher degree of catastrophizing | Up to 15 months | 
| Change from baseline in Generalized Anxiety Disorder-7 | Scores range from 0 to 21 with a higher score indicating more anxiety | Up to 15 months | 
| Change from baseline in PROMIS (Patient-Reported Outcomes Measurement Information System) 16 Questionnaire | This questionnaire is scored on the T-score metric. A higher score indicates a greater amount of whatever concept that the question asks. | Up to 15 months | 
| Change from baseline in Patient Health Questionnaire-9 | Scores range from 0 to 27 with higher scores indicating more depressive symptoms | Up to 15 months | 
| Change from baseline in EQ-5D-5L (EuroQol) | Scores range from 5 to 25 with higher scores indicating more problems. Scores on the visual analogue scale range from 0 to 100 with 100 being the best | Up to 15 months | 
| Change from baseline in McGill Pain Questionnaire | Scores range from 0 to 45 with a higher score indicating more pain. | Up to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Back Pain, Metformin, Placebo