NCT04058717.

Study name	Low nicotine cigarettes plus electronic cigarettes
Methods	RCT: Randomized parallel‐group assignment, 2 X 2 factorial design Setting: USA
Participants	Estimated enrolment 240 participants Inclusion criteria: Meet lifetime diagnostic criteria for a current or lifetime unipolar or bipolar mood disorder  Smoke > 5 cigarettes per day for at least the prior 12 months No serious cigarette smoking quit attempt or use of any FDA‐approved smoking cessation medication in the prior 30 days; no plans to quit smoking within the next 3 weeks Willing to both switch to a different type of cigarette that may contain a different amount of nicotine and to try an EC to substitute for some of their cigarettes Exclusion criteria: Unstable or significant medical condition in the past 3 months  Uncontrolled mental illness or substance abuse, or inpatient treatment for these in the past 6 months or current suicide risk  Use of any non‐cigarette nicotine delivery product or EC  Use illegal drugs/prescription drugs Pregnancy or breastfeeding For a full list see NCT record.
Interventions	EC: type of EC not reported Arm 1 Experimental: NNC cigarettes + high nicotine containing e‐cigarette. Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e‐cigarette with high nicotine e‐liquid. Arm 2 Experimental: NNC cigarettes + zero nicotine containing e‐cigarette. Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e‐cigarette with zero nicotine e‐liquid. Arm 3 Experimental: VLNC cigarettes + high nicotine containing e‐cigarette. Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e‐cigarette with high nicotine e‐liquid. Arm 4 Experimental: VLNC cigarettes + zero nicotine containing e‐cigarette. Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e‐cigarette with zero nicotine e‐liquid.
Outcomes	4, 8, 12 and 16 weeks  Urinary NNAL (4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol)  Exhaled carbon monoxide  Kessler‐6 score measure of serious psychological distress Penn State Cigarette Dependence Index Penn State Electronic Cigarette Dependence Index Cigarette abstinence. No cigarette use in the past 7 days and exhaled carbon monoxide < 6 ppm
Starting date	Actual start date: June 1 2021. Estimated completion date: November 30, 2023
Contact information	Nicolle Krebs, MS 717‐531‐5673, nkrebs@pennstatehealth.psu.edu Jonathan Foulds, PhD 717‐531‐3504, jfoulds@psu.edu
Notes	New to 2022 update