Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DA042074-01 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Pittsburgh | OTHER |
| National Institute on Drug Abuse (NIDA) | NIH |
| University of Massachusetts, Worcester | OTHER |
Not provided
Not provided
The purpose of this study is to examine the efficacy of a specially-constructed crib mattress that delivers gentle vibrations (stochastic vibrotactile stimulation) as a complementary, non-pharmacological intervention for treating drug withdrawal in newborns exposed to opioids in utero.
This study will test the therapeutic efficacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment and hospitalization, and for improving neurobehavioral developmental outcomes in opioid-exposed newborns.
Candidates at-risk for NAS due opioid exposure in utero will be identified to investigators by medical caregiver and/or prescreened using HIPAA Waiver for recruitment (maternal-prenatal; infant-postnatal). Infants will be randomized into either SVS (complementary to standard of care) or Treatment as Usual (TAU), restricted by equipment (mattress) availability. Infants will be enrolled and assigned to a condition within 48 hours post birth and participate throughout hospitalization. Infants assigned SVS will receive daily intervention of continuous intervals of SVS throughout hospitalization using a specially constructed crib mattress that delivers gentle vibrations at preset intervals.
Specific Aim 1. Determine the efficacy of SVS as a non-pharmacological therapy complementary to standard of care for reducing severity and duration of opioid withdrawal in newborns compared to TAU alone. Quantify clinical variables: NAS severity, treatment days, days in hospital, velocity of weight gain, cumulative morphine dose.
Specific Aim 2. Compare neurobehavioral outcomes in fetal drug-exposed infants between infants who received SVS and those who received TAU. Longitudinal outcomes assessment at 6-months and 1 year to test whether early intervention with SVS compared to standard care improves physical, social, emotional and cognitive development.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stochastic Vibrotactile Stimulation (SVS) | Experimental | Infants randomized to this arm will receive daily intervals of continuous SVS (ON) and no SVS (OFF) throughout hospitalization, starting within 48-hrs post birth. SVS will be complementary to standard of clinical care (e.g., clinically-determined pharmacological management; routine parental/volunteer holding; breast and/or bottle feed). |
|
| Treatment as Usual (TAU) | No Intervention | Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stochastic Vibrotactile Stimulation (SVS) | Device | Infant crib mattress will be replaced with a specially constructed mattress (non-commercially available) to provide gentle, stochastic vibration during mattress stimulations. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Administered Morphine Treatment | Number of infants treated with morphine (first line pharmacotherapy at both sites). Number of infants who received pharmacotherapy (met clinical criteria to treat), index of NAS severity (per Finnegan scores). | Participants will be monitored for the duration of their newborn nursery stay, which is an expected mean of 7 days |
| Cumulative Pharmacological Treatment- Morphine Dose | Normalized cumulative morphine dose for infants who completed treatment at respective hospital site (mg/kg). | Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
| Hospitalization Length of Stay | Day of life discharged home for untreated and treated infants who completed hospitalization at study site. Duration of infant hospitalization-Days | Day of life infants discharged home, which is an expected mean of 21 days. |
| Hospitalization Length of Stay for Untreated Infants | Day of life discharged home for untreated infants (infants whose Finnegan scores did not meet criteria to treat) who completed hospitalization at study site. Duration of infant hospitalization-Days | Day of life untreated infants discharged home, which is an expected mean of 21 days. |
| Hospitalization Length of Stay for Treated Infants | Day of life discharged home for treated infants (infants whose Finnegan scores met criteria to treat) who completed hospitalization at study site. Duration of infant hospitalization-Days | Day of life treated infants discharged home, which is an expected mean of 21 days. |
| Length of Pharmacological Treatment-Duration |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Respiratory Rate | Respiratory rate at 1 week of age assessed for about 12 consecutive hours in a subset of subjects | Assess respiratory rate for about 12 consecutive hours at week 1 of infant hospitalization |
Inclusion Criteria: Eligible subjects are infants currently in the NICU or Newborn Nursery at University of Massachusetts Memorial Hospital or at Magee Women's Hospital of UPMC and:
Exclusion Criteria: Eligible infants meeting the inclusion criteria above will be excluded from participation in the study if he/she:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elisabeth B Salisbury, Ph.D. | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh School of Medicine | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33748529 | Background | Bloch-Salisbury E, Bogen D, Vining M, Netherton D, Rodriguez N, Bruch T, Burns C, Erceg E, Glidden B, Ayturk D, Aurora S, Yanowitz T, Barton B, Beers S. Study design and rationale for a randomized controlled trial to assess effectiveness of stochastic vibrotactile mattress stimulation versus standard non-oscillating crib mattress for treating hospitalized opioid-exposed newborns. Contemp Clin Trials Commun. 2021 Feb 11;21:100737. doi: 10.1016/j.conctc.2021.100737. eCollection 2021 Mar. | |
| 35636580 |
| Label | URL |
|---|---|
| Study design and rationale for a randomized controlled trial to assess effectiveness... | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Infants recruited at UMass between March 9, 2017 and February 25, 2020; Infants recruited at Pitt between and August 18, 2017 and March 10, 2020.
Enrollment was terminated early due to Covid-19 in-person study restrictions and unanticipated reduction and relocation of project personnel (208 recruited/220 anticipated enrollment).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Stochastic Vibrotactile Stimulation (SVS) | Infants randomized to this arm will receive daily intervals of continuous SVS (ON) and no SVS (OFF) throughout hospitalization, starting within 48-hrs post birth. SVS will be complementary to standard of clinical care (e.g., clinically-determined pharmacological management; routine parental/volunteer holding; breast and/or bottle feed). Stochastic Vibrotactile Stimulation (SVS): Infant crib mattress will be replaced with a specially constructed mattress (non-commercially available) to provide gentle, stochastic vibration during mattress stimulations. |
| FG001 | Treatment as Usual (TAU) | Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Stochastic Vibrotactile Stimulation (SVS) | Infants randomized to this arm will receive daily intervals of continuous SVS (ON) and no SVS (OFF) throughout hospitalization, starting within 48-hrs post birth. SVS will be complementary to standard of clinical care (e.g., clinically-determined pharmacological management; routine parental/volunteer holding; breast and/or bottle feed). Stochastic Vibrotactile Stimulation (SVS): Infant crib mattress will be replaced with a specially constructed mattress (non-commercially available) to provide gentle, stochastic vibration during mattress stimulations. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | gestational age (weeks) |
| 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 | Number of Participants Administered Morphine Treatment | Number of infants treated with morphine (first line pharmacotherapy at both sites). Number of infants who received pharmacotherapy (met clinical criteria to treat), index of NAS severity (per Finnegan scores). | Analyzed infants: completed hospitalization at respective study site | Posted | Count of Participants | Participants | Participants will be monitored for the duration of their newborn nursery stay, which is an expected mean of 7 days |
|
All-Cause Mortality, Serious and Other adverse events (AE) were obtained for up to 14 months; includes in-hospital and reports obtained post-hospital discharge throughout the follow-up period.
All-Cause Mortality, Serious and Other Adverse events were obtained for both the SVS (intervention) and TAU (control) groups.
Serious AEs reported include medical events that may occur in NICU environments, e.g. cluster necrotizing enterocolitis (NEC).
Inherent AEs routinely assessed via Finnegan were not reported; AEs determined by medical caregiver and/or study safety officer that fell outside scope and/or degree of medical events commonly experienced by subject population.
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 | Stochastic Vibrotactile Stimulation (SVS) | Infants randomized to this arm will receive daily intervals of continuous SVS (ON) and no SVS (OFF) throughout hospitalization, starting within 48-hrs post birth. SVS will be complementary to standard of clinical care (e.g., clinically-determined pharmacological management; routine parental/volunteer holding; breast and/or bottle feed). Stochastic Vibrotactile Stimulation (SVS): Infant crib mattress will be replaced with a specially constructed mattress (non-commercially available) to provide gentle, stochastic vibration during mattress stimulations. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cluster necrotizing enterocolitis | Gastrointestinal disorders | Non-systematic Assessment |
Not provided
Enrollment closed at 208 infants before reaching proposed enrollment of 220 infants due to the administration at UMass reneging support for the project, requiring close out at UMass site. PI and funding support were transferred to complete the project at the UPitt site. Delays in reporting reflect transfer-related project restructuring and reduction in study personnel.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elisabeth B Salisbury, PhD | University of Pittsburgh School of Medicine | 14122465378 | salisburye2@upmc.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 | Dec 7, 2020 | Oct 20, 2022 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009357 | Neonatal Abstinence Syndrome |
| D013375 | Substance Withdrawal Syndrome |
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
For infants who received pharmacotherapy, total days of morphine treatment. |
| Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
| Trajectory of Symptom Severity Among Treated Infants | Days to start morphine treatment based on Finnegan severity scores among infants who met clinical criteria to treat | Day of life infant started morphine treatment |
| Velocity of Weight Gain | Weight loss precedes weight gain in newborns. Days to weight nadir, defined as the lowest weight following birthweight. Velocity of weight gain was measured as days to return to birthweight, i.e., the day on which weight reached or surpassed birthweight following initial weight loss from birth. | Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
| Neurobehavioral Outcomes Assessment | Scores for Cognitive Domain Bayley Scales of Infant and Toddler Development Third Edition. The standardized scores have a mean of 100 and standard deviation (SD) of 15. Scores below 1 SD (= or less than 84) is considered below normal. Scores above 1 SD (>115) represent higher than normal functioning. | 6 month and 12 months of life |
| Bloch-Salisbury E, Rodriguez N, Bruch T, McKenna L, Goldschmidt L. Physiologic dysregulation in newborns with prenatal opioid exposure: Cardiac, respiratory and movement activity. Neurotoxicol Teratol. 2022 Jul-Aug;92:107105. doi: 10.1016/j.ntt.2022.107105. Epub 2022 May 27. |
| 37353324 | Background | Liu VY, Flahive JM, Bloch-Salisbury E. Actigraphy: An Adjunctive Method to Measure Irritability in Opioid-Exposed Newborns. J Nurs Meas. 2024 Oct 24;32(3):467-476. doi: 10.1891/JNM-2023-0020. |
| 37184872 | Result | Bloch-Salisbury E, Wilson JD, Rodriguez N, Bruch T, McKenna L, Derbin M, Glidden B, Ayturk D, Aurora S, Yanowitz T, Barton B, Vining M, Beers SR, Bogen DL. Efficacy of a Vibrating Crib Mattress to Reduce Pharmacologic Treatment in Opioid-Exposed Newborns: A Randomized Clinical Trial. JAMA Pediatr. 2023 Jul 1;177(7):665-674. doi: 10.1001/jamapediatrics.2023.1077. |
| 33348423 | Derived | Pahl A, Young L, Buus-Frank ME, Marcellus L, Soll R. Non-pharmacological care for opioid withdrawal in newborns. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD013217. doi: 10.1002/14651858.CD013217.pub2. |
| Physiologic dysregulation in newborns with prenatal opioid exposure: Cardiac, respiratory and movement activity | View source |
| Actigraphy: An Adjunctive Method to Measure Irritability in Opioid-Exposed Newborns | View source |
| Subsequently met exclusion/withdrawal criteria |
|
| BG001 | Treatment as Usual (TAU) | Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. |
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Birthweight | Mean | Standard Deviation | grams |
|
| OG001 | Treatment as Usual (TAU) | Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. |
|
|
|
| Primary | Cumulative Pharmacological Treatment- Morphine Dose | Normalized cumulative morphine dose for infants who completed treatment at respective hospital site (mg/kg). | Analyzed cohort who received morphine treatment | Posted | Mean | Standard Deviation | mg/kg | Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
|
|
|
|
| Primary | Hospitalization Length of Stay | Day of life discharged home for untreated and treated infants who completed hospitalization at study site. Duration of infant hospitalization-Days | Untreated and treated infants who completed hospitalization at study site. | Posted | Mean | Standard Deviation | day of life discharged home | Day of life infants discharged home, which is an expected mean of 21 days. |
|
|
|
|
| Primary | Hospitalization Length of Stay for Untreated Infants | Day of life discharged home for untreated infants (infants whose Finnegan scores did not meet criteria to treat) who completed hospitalization at study site. Duration of infant hospitalization-Days | Posted | Mean | Standard Deviation | day of life discharged home | Day of life untreated infants discharged home, which is an expected mean of 21 days. |
|
|
|
|
| Primary | Hospitalization Length of Stay for Treated Infants | Day of life discharged home for treated infants (infants whose Finnegan scores met criteria to treat) who completed hospitalization at study site. Duration of infant hospitalization-Days | Posted | Mean | Standard Deviation | day of life discharged home | Day of life treated infants discharged home, which is an expected mean of 21 days. |
|
|
|
|
| Primary | Length of Pharmacological Treatment-Duration | For infants who received pharmacotherapy, total days of morphine treatment. | Analyzed cohort who received morphine treatment | Posted | Mean | Standard Deviation | days | Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
|
|
|
|
| Primary | Trajectory of Symptom Severity Among Treated Infants | Days to start morphine treatment based on Finnegan severity scores among infants who met clinical criteria to treat | Posted | Mean | Standard Deviation | day of life started treatment | Day of life infant started morphine treatment |
|
|
|
|
| Primary | Velocity of Weight Gain | Weight loss precedes weight gain in newborns. Days to weight nadir, defined as the lowest weight following birthweight. Velocity of weight gain was measured as days to return to birthweight, i.e., the day on which weight reached or surpassed birthweight following initial weight loss from birth. | Nadir was obtained in treated and untreated infants who completed hospitalization at study site. Weight gain was obtained only in pharmacologically treated infants; untreated infants were discharged prior to weight gain. | Posted | Mean | Standard Deviation | days | Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days |
|
|
|
| Primary | Neurobehavioral Outcomes Assessment | Scores for Cognitive Domain Bayley Scales of Infant and Toddler Development Third Edition. The standardized scores have a mean of 100 and standard deviation (SD) of 15. Scores below 1 SD (= or less than 84) is considered below normal. Scores above 1 SD (>115) represent higher than normal functioning. | Study infants who participated in follow-up assessments post hospitalization. | Posted | Mean | Standard Deviation | score on a scale | 6 month and 12 months of life |
|
|
|
| Other Pre-specified | Respiratory Rate | Respiratory rate at 1 week of age assessed for about 12 consecutive hours in a subset of subjects | Not Posted | Assess respiratory rate for about 12 consecutive hours at week 1 of infant hospitalization | Participants |
| 0 |
| 105 |
| 1 |
| 105 |
| 0 |
| 105 |
| EG001 | Treatment as Usual (TAU) | Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. | 1 | 103 | 1 | 103 | 0 | 103 |
Not provided
Not provided
| Return to Birthweight |
|
|
| Cognitive Score at 12 months |
|
|