Aim: To evaluate the safety and efficacy of three Vitamin D supplements in Chronic Low back Pain.

Primary Efficacy Objective(s):

·      To compare any change in Cholecalciferol and 25-hydroxy cholecalciferol {25(OH)D} levels after administration of various study formulations.

·      To compare any change in Parathyroid hormone (PTH, intact) levels after administration of various study formulation.

Secondary Efficacy Objective(s):

·      To evaluate pain intensity in patients with CLBP before and after the addition of Vitamin D to standard therapy using a 10-point Visual Analogue Scale (VAS).

·      To evaluate functional disability in patients with CLBP before and after the addition of Vitamin D to the standard therapy using Modified Oswestry Disability Questionnaire (MODQ).

Safety Objective(s):

·         Document the any incidence of hypercalcaemia

–     Mild hypercalcemia: 10.5 to 11.9 mg/dL

–     Moderate hypercalcemia: 12.0 to 13.9 mg/dL

–     Hypercalcemic crisis:14.0 to 16.0 mg/dL

·         Document any incidence of hypervitaminosis D {25(OH)D concentration >150 ng/ml (>375 nmol/l)}

·         Document any incidence of suppression of PTH (intact) levels below the normal range of 14 to 65 pg/mL

·         Document any change in serum inorganic phosphorous {normal range 3.4  to 4.5 mg/dl   (1.12 to 1.45 mmol/L)}

Study Sites:

1.      Out Patient department of Orthopaedics- St. John’s Medical College Hospital, Sarjapura Road, Bangalore-560 034.

2.      Out Patient department of Orthopaedics- Indira Gandhi Institute of Medical Sciences Sheikhpura, Patna 800 014.

3.      Out Patient department of Orthopaedics- Osmania Medical College 5-1-876 Turrebaz Khan Road, Koti, Hyderabad 500 095.

Total Study duration: 6-months.

Treatment & Evaluation Phase: 35-days (Screening to follow-up visit)

Study Description:

This study is a prospective, randomized, open label, multicentre, analytical study consisting of 03 groups of Vitamin D insufficient individuals. Each group consists of 63 patients therefore the total number of patients will be 189. The subjects included are Vitamin D insufficient individuals experiencing CLBP for >03-months.

One group will be treated with Vitamin D3 Orally Disintegrating Strips  60000 IU- once daily for 10 days, the 2^nd group is treated with Nano Carrier Entrapped Vitamin D3 Oral Dispersion 60000 IU once daily for 10 days, and the 3^rd group will be treated with a single dose of Arachitol 6L Injection.

Inclusion Criteria:

i.   Vitamin D insufficient patients of either gender, aged between 18–75 years with CLBP of 03-months or more with or without leg pain.

ii.  Vitamin D insufficiency will be identified with estimation of 25(OH)D in blood. Levels below 29 ng/ ml will be considered as vitamin D insufficiency.

iii. The diagnosis of CLBP would be established based on signs, symptoms and MRI.

iv.  Patients are required to have language competency (English, Telugu, Kanada or Hindi) in order to complete the study related questionnaires which include a Modified Oswestry Disability Questionnaire (MODQ) to measure functional disability, work status, and the use of medication, and a visual analogue scale (VAS) to measure pain intensity.

v.    Patients having a pain score of atleast 05 as assessed on Visual Analogue Scale (VAS) at baseline. 

vi.  Patients are required to have stable pain score for 03-months before recruitment and could be on any oral analgesic therapy.

vii. Patients not responding to any medication and physical therapies.

viii.Record will be made of patient history, physical examination, and laboratory tests.

ix.  Women of childbearing potential are required to receive a highly effective form of contraception.

x.   Subject and legally acceptable representative (LAR) are able to attend all scheduled visits and to comply with all trial procedures.

xi.  All patients will provide signed Informed Consent.

Exclusion Criteria      

i.    Patients who have taken Vitamin D supplementation during past 03-months.

ii.   Patients with a prior radiologically confirmed diagnosis of spondylolisthesis, disc herniation, spinal canal stenosis, vertebral compression fracture, spinal malformation or spinal injury.

iii.  Patients with a past history of spinal surgery.

iv.  Patients with established spinal tuberculosis or other spinal infections, malignancy, rheumatic disorder, osteomalacia, osteoporosis, osteoarthritis and metabolic bone disease (hypo- or hyperparathyroidism).

v.   Patients of diabetes mellitus, epilepsy, psychiatric diseases, substance abuse disorder, chronic renal disease, and medical or surgical disorders affecting Vitamin D metabolism (gastric surgery, chronic liver disease, renal failure, intestinal malabsorption, systemic infections, cancers etc.).

vi.  Neuropathic Pain Conditions are ruled out by using DN4 Questionnaire on screening day.

vii. Malabsorption conditions such as Celiac disease are ruled out by Celiac Disease Questionnaire.

viii. Patients consuming drugs altering bone metabolism like corticosteroid or bisphosphonates.

ix.   Pregnant and lactating mothers and women intending pregnancy.

x.    Patients diagnosed with Illness/ infection on the day of the inclusion.

xi.   Identified as a natural or adopted child of the Investigator, relatives or employee with direct involvement in the proposed study.

Study Endpoints:

Efficacy Endpoints

·         Change from baseline in Cholecalciferol and 25(OH)D level on day-10 and day-30 of the study.

·         To compare any change in PTH (intact) levels after administration of various study formulation.

·         Reduction in pain intensity from baseline at day-10 and day-30 using VAS.

·         Change functional disability from baseline in MODQ at day-10 and day-30.

Safety Endpoints

·         Document incidence of hypercalcaemia, hyper-vitaminosis D, suppression in PTH (intact) level and change in serum inorganic phosphorous

·         Number of participants with adverse events (AEs) from day-01 to day-30.

·         Total number of adverse events

An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.

Study Procedure

·         Screening/Washout Period (Visit 1 — within 3 days prior to treatment initiation)

·         Baseline Phase: (Visit 2 - Day 1 - Treatment Initiation)

·         Follow-up Visit-1(Visit 3- Day 10)

·         End of treatment (Visit 4/week 5- Day 30)

·         Follow-up Period: On completion of the treatment period, a follow up visit will be performed. The patients will be followed-up for a period of up to 20 days from the end of treatment visit.

Rescue Medication:

            Any rescue medication which is taken by the patient will be recorded in the daily diary.

Statistical Methodology:

            Data will be analysed using SPSS V15.0 (Statistical Package for Social Sciences, Version 15.0) package. Data will be given as Mean, SD and N for continuous data and Number and Percentage for categorical data. Comparison of means of 2 groups will be carried out by Student’s unpaired t test for numerical normal data. Fisher Exact Probability tests will be applied to compare percentages for categorical data between 2 groups. Chi square test will be applied to compare percentages of more than 2 groups. Comparison of means of more than 2 groups will be compared by one way ANOVA test. Scheffe post hoc test will be used to compare pair of means after getting significance by ANOVA test. Student’s paired t test and analysis of repeated measures will be applied to compare changes at 2 and more than 2 time points. After checking data for normality, if the data are non-normal, corresponding non parametric tests will be applied to the data. All statistical tests will be two tailed. Alpha (α) Level of Significance will be taken as P<0.05.