Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Colorado State University | OTHER |
Not provided
Not provided
Heart rate variability biofeedback (HRVB) is an biobehavioral intervention involving rhythmic breathing at resonance frequency that stimulates cardiovascular regulatory systems to help individuals better regulate affect and bolster cognitive control. This intervention has already shown its potential as a substance use disorder (SUD) treatment tool, but practical limitations of its accessibility, labor intensiveness, and cost have previously prevented this intervention from going to scale. Second-generation, ambulatory HRVB technology, however, has overcome these limitations and now allows patients to practice HRVB in-the-moment when its needed most. This study is testing the efficacy of second-generation, ambulatory HRVB for the first time with individuals with SUD.
Alcohol and other drug use (AOD) lapses in early substance use disorder (SUD) recovery typically arise from interactions between aversive affective states and stressors that together elicit urges to use. A central goal of first-line cognitive-behavioral SUD treatments is to strengthen affective and cognitive control to increase individuals' ability to override impulses to use AOD. Yet certain automatic physiological processes compromised by SUD dynamically interact with internal affective states and environmental cues to undermine effortful cognitive control and outcompete cognitive goals to avoid substance use.
Heart rate variability biofeedback (HRVB) is a biobehavioral intervention involving rhythmic breathing at resonance frequency (RF) that stimulates the body's baroreflex mechanism to offset these psychophysiological deficits. The autonomic normalization effected by RF breathing is thought to bolster cognitive control efforts by interrupting or dampening automatic-visceral reactions that can undermine treatment gains, and in doing so support better decision-making, motivation, reductions in craving, and shifts in attention allocation.
Previous studies of HRVB have focused on positive behavioral effects that accrue over a series of weeks or months, rather than 'in-the-moment'. These chronic behavior changes, although clinically valuable, are labor and time intensive to elicit, reducing the likelihood of large-scale uptake of the intervention. Further, first-generation HRVB's regular daily practice model is likely to only partially mitigate the intense momentary bouts of emotion dysregulation that are triggers for AOD use in those in early SUD recovery. In contrast, recent studies have demonstrated that a brief exposure to RF breathing in anticipation of psychosocial stress, or during induced stress, helps to control physiological arousal, reduce state anxiety, and improve cognitive performance. It is posited that such bursts of in-the-moment HRVB practice could serve as a potent SUD treatment tool that helps individuals self-regulate emotions when needed most.
Recent advances in the field have given rise to small, lightweight, wearable biosensors that can allow wearers to do HRVB on-the-go. These devices also have the capacity to function as a just-in-time intervention by prompting in-the-moment HRVB practice when autonomic hyperarousal is detected, to buffer salient triggers and urges to use AOD. This research builds on a body of preliminary work speaking to HRVB's potential as an addendum to first-line SUD treatments by exploring for the first time in this disorder this second-generation, ambulatory, HRVB technology. Specific aims of this research include, 1) assessing ambulatory HRVB's uptake by individuals with SUD, 2) testing day-level effects of in-the-moment HRVB practice on affective states and substance use, and 3) testing the accumulative effects of scheduled daily HRVB practice, in-the-moment HRVB practice, and their combination, on substance use.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Heart rate variability biofeedback + treatment as usual | Experimental | 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 | Active Comparator | The control group participated in 8 weeks of treatment as usual only. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Heart rate variability biofeedback + treatment as usual | Device | Heart rate variability biofeedback is a biobehavioral intervention involving rhythmic breathing at resonance frequency (RF) that stimulates the baroreflex and increases heart rate variability. |
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate Variability Biofeedback Engagement | 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 | 8 weeks |
| Day-level Negative Affect | Average day-level score reported; Range = 0-10; higher values denote greater negative affect | 8 weeks |
| Day-level Positive Affect | Average day-level score reported; Range = 0-10; higher values denote greater positive affect | 8 weeks |
| Day-level Craving | Average day-level score reported; Range = 0-10; higher values denote greater craving | 8 weeks |
| Day-level Substance Use | Percent participants reporting any day-level substance use | 8 weeks |
| 8-week Substance Use | Mean percent days abstinent over the 8-week intervention period | 8 weeks |
| Odds Ratio of Within-day Association Between AOD Craving and AOD Use | Within-day association between alcohol and other drug (AOD) craving earlier in the day and the odds of AOD use later that same day | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change Craving | Change in craving measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM). | 8 weeks |
| Change Positive Affect |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| David Eddie, Ph.D. | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114-4714 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41032322 | Derived | Eddie D, Nguyen M, Zeng K, Mei S, Emery N. Heart Rate Variability Biofeedback for Substance Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Dec 1;82(12):1177-1185. doi: 10.1001/jamapsychiatry.2025.2700. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
All enrolled participants were assigned to a group.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Treatment as Usual Only | The control group participated in 8 weeks of treatment as usual only. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Heart Rate Variability Biofeedback + Treatment as Usual | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Five experimental group participants were excluded from the baseline analyses; four failed to comply with the study protocol and one was found to be ineligible after study enrollment. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Heart Rate Variability Biofeedback Engagement | 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 | 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). | Posted | Count of Participants | Participants | 8 weeks |
|
8 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Heart Rate Variability Biofeedback + Treatment as Usual | 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. Heart rate variability biofeedback + treatment as usual: Heart rate variability biofeedback is a biobehavioral intervention involving rhythmic breathing at resonance frequency (RF) that stimulates the baroreflex and increases heart rate variability. Treatment as usual only: Treatment as usual may include any outpatient substance use disorder treatment or mutual-help group participation. |
Not provided
Not provided
Limitations include: (1) a modest sample size and no placebo group, reflecting the phase II stage of the trial; (2) focus on individuals in their first year of abstinence-based SUD recovery, enhancing relevance for this group but limiting generalizability; (3) lack of follow-up; and (4) testing only the hypothesized moderation effect of HRVB on the craving-AOD use relationship, without examining other mechanisms.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Eddie | Massachusetts General Hospital / Harvard Medical School | 6176439194 | deddie@mgh.harvard.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 27, 2023 | May 27, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 29, 2023 | May 27, 2025 | ICF_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Heart rate variability biofeedback + treatment as usual vs. treatment as usual only
Not provided
Not provided
Not provided
Not provided
| Treatment as usual only | Behavioral | Treatment as usual may include any outpatient substance use disorder treatment or mutual-help group participation. |
|
Change in positive affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM).
| 8 weeks |
| Change Negative Affect | Change in negative affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM). | 8 weeks |
| BG001 | Treatment as Usual Only | The control group participated in 8 weeks of treatment as usual only. |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Perceived Stress Scale | Scale range = 0-25; higher scores indicate greater stress | Mean | Standard Deviation | Units on a scale |
|
| Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety 6a | Scale range = 6-30; higher scores indicate greater anxiety | Mean | Standard Deviation | Units on a scale |
|
| Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression 6a | Scale range = 6-30; higher scores indicate greater depression | Mean | Standard Deviation | Units on a scale |
|
| OG001 | Treatment as Usual Only | The control group participated in 8 weeks of treatment as usual only. |
|
|
| Primary | Day-level Negative Affect | Average day-level score reported; Range = 0-10; higher values denote greater negative affect | 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). | Posted | Mean | Standard Deviation | Scores on a scale | 8 weeks |
|
|
|
|
| Primary | Day-level Positive Affect | Average day-level score reported; Range = 0-10; higher values denote greater positive affect | 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). | Posted | Mean | Standard Deviation | Scores on a scale | 8 weeks |
|
|
|
|
| Primary | Day-level Craving | Average day-level score reported; Range = 0-10; higher values denote greater craving | 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). | Posted | Mean | Standard Deviation | Scores on a scale | 8 weeks |
|
|
|
|
| Primary | Day-level Substance Use | Percent participants reporting any day-level substance use | 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). | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
|
| Primary | 8-week Substance Use | Mean percent days abstinent over the 8-week intervention period | 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). | Posted | Mean | Standard Deviation | percentage of days abstinent | 8 weeks |
|
|
|
|
| Primary | Odds Ratio of Within-day Association Between AOD Craving and AOD Use | Within-day association between alcohol and other drug (AOD) craving earlier in the day and the odds of AOD use later that same day | 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. | Posted | Number | Odds ratio | 8 weeks |
|
|
|
| Secondary | Change Craving | Change in craving measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM). | Not Posted | Mar 2026 | 8 weeks | Participants |
| Secondary | Change Positive Affect | Change in positive affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM). | Not Posted | Mar 2026 | 8 weeks | Participants |
| Secondary | Change Negative Affect | Change in negative affect measured by ecological momentary assessment over the 8-week intervention period, modeled using time-varying effects modeling (TVEM). | Not Posted | Mar 2026 | 8 weeks | Participants |
| 0 |
| 70 |
| 0 |
| 70 |
| 0 |
| 70 |
| EG001 | Treatment as Usual Only | The control group participated in 8 weeks of treatment as usual only. Treatment as usual only: Treatment as usual may include any outpatient substance use disorder treatment or mutual-help group participation. | 0 | 50 | 0 | 50 | 0 | 50 |
Not provided
Not provided
Main effect of treatment group
| Superiority |