Magnesium Oral Supplementation for Acute Non-specific Low Back Pain
Condition: Low Back Pain; Acute Pain
MeSH terms: Back Pain; Low Back Pain; Acute Pain
Study type: Interventional

Summary: 
      Acute non-specific low back pain (LBP) is one of the most common complaints at the emergency
      department. It is more prevalent in countries with high-income economies, where 60-80% of the
      population report back pain at some point in their life. Numerous medication options are
      available for acute LBP relief such as non-steroid anti-inflammatory drugs (NSAIDs),
      myorelaxant drugs, opioids, and benzodiazepines. Magnesium is a physiological
      voltage-dependent blocker of N-methyl-D-aspartate NMDA)-coupled channels that can influence
      inflammatory pain and neuropathic pain through several different mechanisms. In this study
      the investigators aimed to investigate the effect of magnesium oral supplementation for acute
      low back pain.
    

Detailed description: 
      This study was conducted at our emergency department between June 2018 and March 2020 after
      receiving approval from our institutions' ethics committee (2018/1330). This study was
      registered as a randomized controlled trial with the US National Institute of Health
      (clinical trials.gov). We conducted a three-arm, prospective randomized open label clinical
      trial to compare isolated NSAID group, NSAID with paracetamol group and NSAID with oral
      magnesium supplementation group (described below) for treatment of acute LBP. Patients were
      included after providing informed consent predicated on their understanding of expected
      complications and treatment outcomes. Consolidate Standards of Reporting Trials (CONSORT)
      guidelines were followed reporting the results of the study Patients from a single university
      hospital were recruited for this study between June 2018 and March 2020. Inclusion criteria
      were defined as (1) age>18 years old, (2) duration of symptoms <2 weeks and (3) functionally
      impairing LBP which we defined as a score of > 5 on Roland-Morris Disability Questionnaire
      (RMDQ).

      Exclusion criteria included (1) age>65 years old, (2) history of trauma, (3) presence of
      radicular pain physical examination which was defined as pain radiating below the gluteal
      folds, (4) history of primary vertebral tumor or metastasis, (4) patients who were pregnant
      or lactating, (5) presence of any contraindication or allergy to investigational medications,
      (6) history of chronic analgesic use, (7) history of autoimmune diseases or inflammatory
      rheumatic disorders, (8) history of cardiopulmonary restrictions, severe kidney or liver
      function disorders and (9) history of prior surgery of lumbar spine.

      We based our sample size calculation assumptions on a recently published clinical trial [11]
      and widely accepted minimum clinically important improvement of 5 points on the RMDQ.(14)
      With alpha and beta values were set at 0.05 and 0.20 respectively, sample size calculation
      revealed that 50 patients were needed in each study group. To account for protocol
      violations, lost-to-follow-up and to ensure sufficient power for the intention to treat
      analysis (in previous work, up to 1/3 of enrolled patients did not use the investigational
      medication), we enrolled 80 patients for each group.

      A computer generated random list was established with an online sequencer
      (www.random.org/sequences) according to which participants were randomly assigned to one of
      three study groups with 1:1:1 allocation ratio. Group A included isolated NSAID treatment and
      received 400 mg etodolac twice a day. Group B included NSAID and magnesium treatment and
      received a combination of 400 mg etodolac twice a day with 365 mg oral magnesium
      supplementation once a day. Group C included NSAID and paracetamol treatment and combination
      of 400 mg etodolac twice a day with 500 mg paracetamol twice a day was administered to the
      participants of this group (Figure-1). We effort to prevent the placebo effect by comparing
      the NSAID + magnesium therapy with both a NSAID plus paracetamol therapy and an isolated
      NSAID therapy. Treatment was performed by two authors (S.B and K.Ş) and patients were
      followed-up by same authors throughout the study. External medication was not allowed with
      the exception of topical analgesics. Patients who received any intravenous or intramuscular
      analgesia during the treatment period were excluded from study. Co-medications for any
      accompanying chronic condition (diabetes, hypertension etc.) were unchanged.

      Clinical evaluation of participants was performed at first admission to emergency department,
      at 4th and 10th days after the initiation of designated treatment. Outcome measures included
      pain, mobility of lumbar spine and functional outcome. Pain intensity was assessed using a
      visual analogue scale (VAS). Lumbar spine mobility was assessed using the "finger to floor"
      test. Participants were asked to stand on erect posture with knees extended and then to bend
      forward in an attempt to reach for the floor with their fingertips without losing knee
      extension. Distance between patient's fingertips and the floor was then measured with a
      measuring tape. Functional outcome was evaluated with Roland-Morris Disability Questionnaire
      (RMDQ) score. RMDQ is a 24-item LBP functional scale and is recommended for research
      purposes. Higher scores signify greater low back-related functional impairment. An
      improvement of 5 points was considered clinically significant.
    

Intervention name(s): Magnesium; NSAID; paracetamol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Patients were treated with etodolac 400mg twice a day plus magnesium oral supplementation once a day for acute low back pain and clinical evaluation of participants was performed at first admission to emergency department, at 4th and 10th days after the initiation of designated treatment; Patients were treated with etodolac 400mg twice a day for acute low back pain and and clinical evaluation of participants was performed at first admission to emergency department, at 4th and 10th days after the initiation of designated treatment; Patients were treated with etodolac 400mg twice a day plus 500mg paracetamol twice a day paracetamol for acute low back pain and and clinical evaluation of participants was performed at first admission to emergency department, at 4th and 10th days after the initiation of designated treatment
Other intervention name(s): NSAID plus magnesium group; Isolated non-steroid anti-inflammatory group; NSAID plus paracetamol group
Intervention MeSH terms: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment