A Randomized, Controlled, Noninferiority Trial Comparing Vitamin B12 Monotherapy Versus Combination Multinutrient Therapy with Vitamin B12 for Efficacy in Treatment of Infantile Tremor Syndrome.

Abstract

To compare the mean Likert (caregiver impression of change) and CAPUTE scores in children with ITS treated with daily injectable vitamin B12 alone versus injectable vitamin B12 with other multinutrients at 1 wk and 1 mo of therapy. This was an open-label, active-controlled, assessor-blinded, noninferiority, randomized clinical trial. The participants included children aged 3 mo to 2 y with infantile tremor syndrome. Children were randomized to receive either 1mg of daily injectable vitamin B12 or 1mg of daily injectable vitamin B12 with other multinutrients (B12 + MV). Primary outcome measure was the mean Likert score in the two arms at 1 wk. Secondary outcome measures were mean change in CAPUTE scores at 1 wk of therapy; and mean change in CAPUTE and Vineland Social Maturity Scale (VSMS) scores after 1 mo of treatment. Seventy-two (N = 72) of the 160 screened were enrolled and randomized. The mean (SD) Likert score in the B12 group (n = 38) was 16.1 (3.7) and in the B12 + MV group (n = 34) was 14.9 (3.7); p = 0.237. Mean (SD) change in CAPUTE (CAT/CLAMS) at 1 mo in the groups was not statistically different. The mean (SD) change in social quotient in the B12 monotherapy group, 35.0 (20.7) was significantly higher than the B12 + multinutrient group 23.5 (15.4); p=0.01. Injectable vitamin B12 monotherapy in ITS resulted in an improvement that was noninferior to combination multinutrient therapy, strongly supporting vitamin B12 deficiency as the cause of infantile tremor syndrome. The trial was registered at CTRI.org (CTRI/2018/05/013841).