Development of an Algorithm That Predicts Hypoventilation Due to an Opioid Overdose

Opioid-Related Disorders Clinical Trial

Official title:

Development of an Algorithm That Predicts Hypoventilation Due to an Opioid Overdose

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03845699
• Other study ID #: 20183438,18C.7
• Status: Recruiting
• Start date: May 15, 2019
• Est. completion date: May 14, 2020

Study information

• Verified date: May 2019
• Source: RTM Vital Signs, LLC
• Contact: Stephen McNulty, DO
• Phone: 215-955-6161
• Email: Stephen.McNulty[@]Jefferson.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

RTM Vital Signs, LLC is developing a miniature wearable tracheal sound sensor that communicates with a cell phone containing a machine-learning diagnostic algorithm designed to detect and predict the onset of mild, moderate, and severe hypoventilation (respiratory depression) due to an opioid overdose. The purpose of this clinical trial is to develop/validate diagnostic algorithms capable of detecting/predicting the onset of hypoventilation induced by a controlled intravenous infusion of fentanyl. The wearable sensor and algorithms will provide a series of alerts and alarms to the person, caregiver, and/or emergency personnel.

Description:

More than 64,000 Americans died from a drug overdose in 2016 and drug overdose is now the most common cause of death for people under 50 years old in the United States. The purpose of this study is to design a wearable tracheal sound sensor and develop an experimental computer program (diagnostic algorithm) that can accurately detect and predict the onset of mild, moderate, and severe hypoventilation (slow and shallow breathing) due to an opioid (fentanyl) overdose

Opioid pain medications routinely cause a person's breathing to become slower and shallower, leading to an increased amount of carbon dioxide and decreased amount of oxygen in the bloodstream. Microphone trachea sound sensors will be used to measure and record sounds produced by air movement in and out of a person's trachea (windpipe) during inhalation and exhalation. Blood will be frequently sampled from a catheter placed within a wrist artery to measure the concentration of carbon dioxide and oxygen. An intravenous infusion of fentanyl will be used to decrease the person's respiratory rate and depth of breathing over a 1 to 3 hour period. Other sensors will be used to accurately measure and record the person's respiratory rate, tidal volume, hemoglobin oxygen saturation, electrocardiogram, blood pressure, temperature, body activity level, and body position. Each sensor's output signal will be processed and filtered to enhance the signal-to-noise ratio. The Trachea Sound Sensor and reference respiratory sensor information will be used to develop/validate risk-index algorithms that can recognize a significant change in an individual's "normal or baseline" pattern of respiratory rate, tidal volume, body activity, and body position. The hypoventilation monitoring system will not require previous knowledge of an individual's age, height, weight, model of the respiratory tract, or external calibration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 14, 2020
• Est. primary completion date: May 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Healthy women/men between 18 and 40 years of age.

2. Negative history of drug or alcohol abuse.

3. Negative history of cigarette smoking in previous 6 months.

4. Negative history of active cardiac, vascular, pulmonary, renal, hepatic, nervous, metabolic or immune disease.

5. BMI < 30

Exclusion Criteria:

1. Age < 18 years and > 40 years.

2. Pregnant or planning to become pregnant.

3. Positive history drug or alcohol abuse.

4. Positive drug screen for opioids, benzodiazepines, hypnotics.

5. Positive Drug Abuse Screening Test result (score of 6 or greater).

6. BMI > 30

7. History of sleep apnea.

8. History of cigarette smoking in previous 6 months.

9. History of difficult airway during anesthesia management.

10. History of allergy or skin sensitivity to tape, silicone, fentanyl, chlorhexidine.

Related Conditions & MeSH terms

• Drug Overdose
• Hypoventilation
• Opioid-Related Disorders

Intervention

Device:
• Diagnostic algorithms that detects/predicts hypoventilation
Produce mild and moderate respiratory depression (hypoventilation) using a controlled intravenous infusion of fentanyl while measuring/recording respiratory rate, tidal volume, body activity, and body position.

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
RTM Vital Signs, LLC	Thomas Jefferson University

Country where clinical trial is conducted

United States, 

References & Publications (19)

Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012 Jul 12;367(2):146-55. doi: 10.1056/NEJMra1202561. Review. — View Citation

Bureev AS, Dikman EY, Zhdanov DS, Zemlyakov IY, Kutsov MS. Mathematic Model for Spectral Characteristics of Respiratory Sounds Registered in Trachea Region. Global Journal of Pure and Applied Mathematics. 2016;12(5):4569-4578.

Chen G, de la Cruz I, Rodriguez-Villegas E. Automatic lung tidal volumes estimation from tracheal sounds. Conf Proc IEEE Eng Med Biol Soc. 2014;2014:1497-500. doi: 10.1109/EMBC.2014.6943885. — View Citation

Harper VP, Pasterkamp H, Kiyokawa H, Wodicka GR. Modeling and measurement of flow effects on tracheal sounds. IEEE Trans Biomed Eng. 2003 Jan;50(1):1-10. — View Citation

Jin F, Goh DY, Louis IM. An Enhanced Respiratory Rate Montoring Method for Real Tracheal Sound Recordings. 17 European Signal Processing Conference. 2009:642- 645.

Kraman SS, Wodicka GR, Pressler GA, Pasterkamp H. Comparison of lung sound transducers using a bioacoustic transducer testing system. J Appl Physiol (1985). 2006 Aug;101(2):469-76. Epub 2006 Apr 20. — View Citation

Lu BY. Unidirectional Microphone based Wireless Recorder for the Respiration Sound. J Bioengineer & Biomedical Sci. 2016;6(3).

Mildh LH, Scheinin H, Kirvelä OA. The concentration-effect relationship of the respiratory depressant effects of alfentanil and fentanyl. Anesth Analg. 2001 Oct;93(4):939-46. — View Citation

O'Croinin D, Ni Chonghaile M, Higgins B, Laffey JG. Bench-to-bedside review: Permissive hypercapnia. Crit Care. 2005 Feb;9(1):51-9. Epub 2004 Aug 5. Review. — View Citation

Penzel T, Sabil A. The use of tracheal sounds for the diagnosis of sleep apnoea. Breathe (Sheff). 2017 Jun;13(2):e37-e45. doi: 10.1183/20734735.008817. Review. — View Citation

Pérus O, Marsot A, Ramain E, Dahman M, Paci A, Raucoules-Aimé M, Simon N. Performance of alfentanil target-controlled infusion in normal and morbidly obese female patients. Br J Anaesth. 2012 Oct;109(4):551-60. doi: 10.1093/bja/aes211. Epub 2012 Jun 24. — View Citation

Ramsay MA, Usman M, Lagow E, Mendoza M, Untalan E, De Vol E. The accuracy, precision and reliability of measuring ventilatory rate and detecting ventilatory pause by rainbow acoustic monitoring and capnometry. Anesth Analg. 2013 Jul;117(1):69-75. doi: 10.1213/ANE.0b013e318290c798. Epub 2013 Apr 30. — View Citation

Reyes BA, Reljin N, Chon KH. Tracheal sounds acquisition using smartphones. Sensors (Basel). 2014 Jul 30;14(8):13830-50. doi: 10.3390/s140813830. — View Citation

Shafer SL, Varvel JR, Aziz N, Scott JC. Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. Anesthesiology. 1990 Dec;73(6):1091-102. — View Citation

Stuth EA, Stucke AG, Zuperku EJ. Effects of anesthetics, sedatives, and opioids on ventilatory control. Compr Physiol. 2012 Oct;2(4):2281-367. doi: 10.1002/cphy.c100061. Review. — View Citation

Vannucci RC, Towfighi J, Brucklacher RM, Vannucci SJ. Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat. Pediatr Res. 2001 Jun;49(6):799-803. — View Citation

Volkow ND, Collins FS. The Role of Science in Addressing the Opioid Crisis. N Engl J Med. 2017 Jul 27;377(4):391-394. doi: 10.1056/NEJMsr1706626. Epub 2017 May 31. — View Citation

Yadollahi A, Moussavi ZM. Acoustical respiratory flow. A review of reliable methods for measuring air flow. IEEE Eng Med Biol Mag. 2007 Jan-Feb;26(1):56-61. Review. — View Citation

Yu L, Ting CK, Hill BE, Orr JA, Brewer LM, Johnson KB, Egan TD, Westenskow DR. Using the entropy of tracheal sounds to detect apnea during sedation in healthy nonobese volunteers. Anesthesiology. 2013 Jun;118(6):1341-9. doi: 10.1097/ALN.0b013e318289bb30. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Sensitivity and Specificity of Detecting/Predicting the Onset of Mild Hypoventilation due to an Opioid Overdose	The investigators will evaluate the risk-index algorithm's ability to detect/predict at which point during the standardized fentanyl infusion protocol does mild hypoventilation actually occur. Calculate the percent sensitivity and specificity of detecting/predicting the onset of mild hypoventilation (PaCO2- 45 to 50 mm Hg) due to a fentanyl overdose.	1 to 3 hours
Primary	Percent Sensitivity and Specificity of Detecting/Predicting the Onset of Moderate Hypoventilation due to an Opioid Overdose	The investigators will evaluate the risk-index algorithm's ability to detect/predict at which point during the standardized fentanyl infusion protocol does moderate hypoventilation actually occur. Calculate the percent sensitivity and specificity of detecting/predicting the onset of mild hypoventilation (PaCO2- 51 to 60 mm Hg) due to a fentanyl overdose.	1 to 3 hours
Primary	Percent Sensitivity and Specificity of Detecting/Predicting the Onset of Severe Hypoventilation due to an Opioid Overdose	The investigators will evaluate the risk-index algorithm's ability to detect/predict at which point during the standardized fentanyl infusion protocol does severe hypoventilation actually occur. Calculate the percent sensitivity and specificity of detecting/predicting the onset of severe hypoventilation (PaCO2 > 60 mm Hg) due to a fentanyl overdose.	1 to 3 hours
Secondary	Absolute Difference Between Trachea Sound Sensor's Measurements and Reference Sensor Measurements	Correlation between the trachea sound sensor's measurements and the reference sensor measurements of respiratory rate, tidal volume, activity level, and body position during an intravenous infusion of fentanyl (Bland-Altman plot of absolute difference).	1 to 3 hours