Trial Outcomes & Findings for Heart Rate Variability Biofeedback for Substance Use Disorder: A Randomized Clinical Trial (NCT NCT05454657)
NCT ID: NCT05454657
Last Updated: 2025-12-26
Results Overview
Number of participants with ≥50% daily-practice adherence to the study practice target of 15 minutes per day, inclusive of scheduled and self-initiated HRVB practice
COMPLETED
NA
120 participants
8 weeks
2025-12-26
Participant Flow
This was a phase II, randomized clinical trial involving 8 weeks of outpatient treatment. Enrollment occurred virtually in the US from January 4 2023 to June 2024. Of 238 potential participants assessed, 120 treatment-seeking participants with an SUD were randomized.
All enrolled participants were assigned to a group.
Participant milestones
| Measure |
Heart Rate Variability Biofeedback + Treatment as Usual
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
Treatment as Usual Only
The control group participated in 8 weeks of treatment as usual only.
|
|---|---|---|
|
Overall Study
STARTED
|
70
|
50
|
|
Overall Study
COMPLETED
|
65
|
50
|
|
Overall Study
NOT COMPLETED
|
5
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Heart Rate Variability Biofeedback for Substance Use Disorder: A Randomized Clinical Trial
Baseline characteristics by cohort
| Measure |
Heart Rate Variability Biofeedback + Treatment as Usual
n=65 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback (HRVB) practice using the Lief HRVB Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 10mins of scheduled HRVB practice daily, and 3) do at least 5mins per day of HRVB practice in-the-moment when negative affect/craving arose, or in response to just-in-time prompts to do brief bursts of HRVB when the device sensed autonomic arousal indicative of stress.
|
Treatment as Usual Only
n=50 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Total
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.18 Years
STANDARD_DEVIATION 12.08 • n=30 Participants
|
46.18 Years
STANDARD_DEVIATION 11.04 • n=30 Participants
|
46.18 Years
STANDARD_DEVIATION 11.59 • n=60 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=30 Participants
|
29 Participants
n=30 Participants
|
69 Participants
n=60 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=30 Participants
|
21 Participants
n=30 Participants
|
46 Participants
n=60 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=30 Participants
|
2 Participants
n=30 Participants
|
3 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
2 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=30 Participants
|
4 Participants
n=30 Participants
|
11 Participants
n=60 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=30 Participants
|
44 Participants
n=30 Participants
|
95 Participants
n=60 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
4 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=30 Participants
|
6 Participants
n=30 Participants
|
10 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
61 Participants
n=30 Participants
|
44 Participants
n=30 Participants
|
105 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Perceived Stress Scale
|
14.83 Units on a scale
STANDARD_DEVIATION 2.97 • n=30 Participants
|
14.20 Units on a scale
STANDARD_DEVIATION 3.30 • n=30 Participants
|
14.56 Units on a scale
STANDARD_DEVIATION 3.12 • n=60 Participants
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety 6a
|
16.20 Units on a scale
STANDARD_DEVIATION 5.76 • n=30 Participants
|
16.35 Units on a scale
STANDARD_DEVIATION 5.19 • n=30 Participants
|
16.26 Units on a scale
STANDARD_DEVIATION 5.50 • n=60 Participants
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression 6a
|
14.71 Units on a scale
STANDARD_DEVIATION 6.48 • n=30 Participants
|
13.72 Units on a scale
STANDARD_DEVIATION 5.47 • n=30 Participants
|
14.28 Units on a scale
STANDARD_DEVIATION 6.06 • n=60 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Number of participants with ≥50% daily-practice adherence to the study practice target of 15 minutes per day, inclusive of scheduled and self-initiated HRVB practice
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Heart Rate Variability Biofeedback Engagement
|
0 Participants
|
15 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Average day-level score reported; Range = 0-10; higher values denote greater negative affect
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Day-level Negative Affect
|
3.36 Scores on a scale
Standard Deviation 2.13
|
2.96 Scores on a scale
Standard Deviation 2.07
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Average day-level score reported; Range = 0-10; higher values denote greater positive affect
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Day-level Positive Affect
|
5.02 Scores on a scale
Standard Deviation 1.92
|
5.26 Scores on a scale
Standard Deviation 1.97
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Average day-level score reported; Range = 0-10; higher values denote greater craving
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Day-level Craving
|
2.25 Scores on a scale
Standard Deviation 2.77
|
2.32 Scores on a scale
Standard Deviation 2.65
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Percent participants reporting any day-level substance use
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Day-level Substance Use
|
5 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: An additional three participants were excluded from the within-treatment EMA analyses because they completed \<10% of surveys (final within treatment n=112; 64 experimental; 48 controls).
Mean percent days abstinent over the 8-week intervention period
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
8-week Substance Use
|
90.33 percentage of days abstinent
Standard Deviation 16.99
|
91.79 percentage of days abstinent
Standard Deviation 18.03
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: To test the moderating effects of HRVB on the within-day associations between craving and AOD use, we estimated a Bayesian logistic multilevel model with an unstructured variance-covariance matrix where craving earlier in the day predicted AOD use later that same day (L1; lagged within-person). The focal effect of interest was a cross-level interaction between craving earlier in the day (L1) and treatment condition (L2) predicting AOD use later that same day.
Within-day association between alcohol and other drug (AOD) craving earlier in the day and the odds of AOD use later that same day
Outcome measures
| Measure |
Treatment as Usual Only
n=48 Participants
The control group participated in 8 weeks of treatment as usual only.
|
Heart Rate Variability Biofeedback + Treatment as Usual
n=64 Participants
The experimental group participated in 8 weeks of Heart Rate Variability Biofeedback practice using the Lief Heart Rate Variability Biofeedback Smart Patch and smartphone app + treatment as usual. Participants were asked to, 1) wear the Lief Smart Patch for at least 8 hours per day, 2) do 15mins of scheduled Heart Rate Variability Biofeedback practice daily, and 3) use it as needed in response to negative affect in-the-moment.
|
|---|---|---|
|
Odds Ratio of Within-day Association Between AOD Craving and AOD Use
|
1.00 Odds ratio
|
0.84 Odds ratio
|
SECONDARY outcome
Timeframe: 8 weeksChange in craving measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 8 weeksChange in positive affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 8 weeksChange in negative affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM).
Outcome measures
Outcome data not reported
Adverse Events
Heart Rate Variability Biofeedback + Treatment as Usual
Treatment as Usual Only
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. David Eddie
Massachusetts General Hospital / Harvard Medical School
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place