Study design and patients
This research was conducted as a randomized placebo-control clinical trial (RCT) study. Forty-four patients with episodic migraine participated (including 42 female and 2 males) from April to September 2021 at the Tehran University of medical Sciences (TUMS), Tehran, Iran. Inclusion criteria of this research were including age 20-50, body mass index (BMI) 25-35, any of disorders such as cancer, diabetes, thyroid disorders, liver or renal disease, cardiovascular disorders or inflammatory condition, no supplements consumption, special activity and specific diet at least in last 3 months and diagnosis of episodic migraine based on International Headache Society criteria by the neurologist. Exclusion criteria of the study included pregnancy during trial, allergic reaction to curcumin, any alternation in routine treatment and any inflammatory diseases or headache attacks leading to more than 2 weeks use of analgesics.
At the baseline, written informed consent approved by the TUMS ethics committee, was obtained from all participants. The goals, benefits and potential risks of the present study were explained and they were free to leave the trial at any time during the study. The baseline data, medical history, medications, headache frequencies, headache duration based on participants’ reports were recorded at the first and end of the trial. The pain severity was record using Visual Analogue Scale (VAS) measurement.
To determine of compliance, patients were contacted per 2 weeks to ask about supplements consumption or side effects. Less than 90% consumption of the total supplements or placebo at the end of the study was define as non-compliant. Generally, 2 patients in control group withdrew the research due to unwillingness to cooperate.
The current study was approved by the Ethics Committee of TUMS (ID: IR.TUMS.MEDICINE.REC.1399.190) and registered in Iranian Registry of Clinical Trials (IRCT) (ID: IRCT20160626028637N2). This study adheres to CONSORT guidelines.
Nano- curcumin supplementation
We used stratified randomization to control of gender and BMI variables. The sample size was determined by the formula. The participants divided into 2 groups by Permuted Block Randomization method. In each groups of the study 22 patients including 21 women and 1 man were entered. The two groups of the trial defined as: I) the nano-curcumin group (receiving nano-curcumin supplement) and II) the control group (receiving the placebo). The participants in group 1 take 80 mg nano-curcumin included two capsules 40 mg/day and the control group received nano-curcumin placebo containing oral paraffin oil, 2 capsule/day. The period of supplementation was 2 months. The nano-curcumin and placebo capsules were similar in color, size and shape. In addition, the nano-curcumin or placebo capsules were coded by a third person.
Measurement of serum concentration of adipokines
At baseline and after 2-month intervention, 10 ml blood samples were taken from participants. Then, serum of patients was collected after10 minutes centrifugation at 3000 RPM and stored at -80°C for subsequent measurements of resistin, visfatin and MCP-1 levels which conducted by the ELISA method (Mediagnost, Germany) based on kit protocol.
Clinical sign of headache recording
At the baseline and end of the trial, the headache frequencies as number of attacks per week as well as headache attacks duration as average hours of headache were recorded based on patient self-reports. The VAS measurement was used to pain severity recording at the start and end of the 2-month intervention. According to VAS scale, the patients rated their pain (scoring 0 -10). VAS divides the pain severity into five categories as define 0: No pain, 1-3: Mild pain, 4-6: Moderate pain, 7-9: Sever pain and 10: Worst pain (22).
Statistical analysis
The data transferred to SPSS software version 22 for analysis. The normality of data was examined by the Kolmogorov-Smirnov distribution test. The Paired t-test and Independent t test were used for comparison of within and between groups of normal data respectively. Wilcoxon test and Mann–Whitney U test were used respectively for within and between group comparison of data not normally distributed. Chi-squared test was used to compare qualitative variables. ANCOVA test was used to remove the effect of confounding variables. Data is expressed as mean ± Standard Error (SEM). The P value≤ 0.05 was accepted as a statistically significant difference. the intention to treat method was used to replace missing data.