Table 7. Melatonin supplementation trials: protocols and clinical outcomes in individuals with complete cervical SCI.

Study	Protocol	Subjective sleep outcomes	Objective sleep outcomes	Other outcomes	Post-supplementation melatonin values
Spong et al.50	3 mg qhs for 2 weeks	→ (KSS,BNSQ)	→ (PSG)	NA	↑ (undetectable vs. >50 pg/ml before bed-time)
Spong et al.47	Cross-over trial 3 weeks of 3 mg qhs and placebo	→ (sleep diary)	↑ (only NREM1/2 on PSG)	→ (HADS, POMS, AQoL)	↑ (4.0 pg/ml vs. 10128.8 pg/ml 1 h before bed-time)
Zeitzer et al.48*	Cross-over trial 3 weeks of 8 mg of ramelteon qhs and placebo	→ (sleep diary)	→ (WA)	→ (SF-36 subscale scores)	NA
Kostvoski et al.51	Cross-over trial of 4 days of 2 mg qhs and placebo	NA	NA	→ (hemostatic factors)**	↑ (peak concentrations overnight approached 2000–2500 pg/ml)
Kostvoski et al.53	2 mg qhs or placebo	NA	NA	Normalized 24-h expression profile of clock genes***	↑ (10– 500-time increase from baseline overnight)

The protocol reports the dose of melatonin unless otherwise stated. Outcomes are reported using an arrow, with the direction of the arrow giving the difference with respect to placebo (in cross-over trials) or baseline (Spong et al.⁵⁰) measurements (↑ = increased, → = no difference, ↓ = decreased). The outcome measurements are given in parentheses. KSS, Karolinska Sleepiness Scale; BNSQ, Basic Nordic Sleep Questionnaire; PSG, polysomnography; WA, wrist actigraphy; HADS, Hospital Anxiety and Depression Scale; POMS, Profile of Mood States; AQoL, Assessment of Quality of Life; SF-36, Short-Form Health Survey; NA, not assessed; NREM1, non-rapid eye movement sleep stage 1; NREM2; non-rapid eye movement sleep stage 2.

*Zeitzer et al.⁴⁸ included individuals with incomplete cervical SCI with absent melatonin profiles.

**The hemostatic factors included prothrombin fragment 1+2, vWF, D-dimer, tissue factor pathway inhibitor, plasminogen activator inhibitory type 1.

***The clock genes included PER1, PER2, BMAL1, REV-ERB.