Effects of Sleep Disruption on Drug Response

The central scientific premise of the proposed study is that sleep disruption (SD) will influence individuals' subjective response to blinded medication administration. The investigators further believe these responses will vary among patients who have chronic low back pain (CLBP) vs. healthy controls, and that sex will moderate effects.

The proposed study evaluates whether CLBP patients' subjective responses to study medication administration are altered by SD. The investigators focus on two outcome domains: abuse liability (i.e., drug liking and valuation) and response to pain testing.

The investigators propose a mixed between-within randomized crossover human-laboratory experiment that investigates placebo-controlled effects of study medication on 1) abuse liability metrics (Drug Liking and Monetary Valuation) and 2) response to laboratory-evoked standardized pain measures, after one night of uninterrupted sleep (US) and again after one night of SD. The investigators will recruit both CLBP patients(*) and healthy controls (N = 60).

(*) We originally aimed to accrue 60 subjects with CLBP. However, we have been granted approval by the National Institute on Drug Abuse (NIDA) to reduce expectations for the target N for the CLBP cohort. We are no longer expected to recruit N=60 CLBP participants; this is a COVID-19 modification, and we are not required to re-do a power analysis.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Low Back Pain, Recurrent
• Intervention / Treatment: Drug: Within-Subject test of blinded study medication

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael T. Smith, PhD; Phone Number: 410-550-9059; Email: msmith62@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins School of Medicine
      • Contact: Michael T Smith, Ph.D.; Phone Number: 410-550-9059; Email: msmith62@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

General Inclusion Criteria:

• 18-60 years old
• Less than 2 servings/day of caffeinated beverages and willing to discontinue 3 days prior to admission.

CLBP-Specific Inclusion Criteria:

• Have a physician-confirmed diagnosis of CLBP
• Report chronic low back pain.

Exclusion Criteria:

General Exclusion Criteria:

• BMI >40
• Significant medical or psychiatric morbidity within 6 months or lifetime history of bipolar disorder, psychotic disorder, seizure disorder
• Lifetime history of opioid use disorder
• Clinically significant abnormal complete blood count or comprehensive metabolic profile
• Any contraindicated medical condition (status asthmaticus; chronic obstructive pulmonary disease; reduced respiratory function; hypotension; hypertension; impairment of hepatic, pulmonary or renal functions; myxedema or hyperthyroidism; adrenocortical insufficiency; gastrointestinal obstruction; gall bladder disease; acute alcoholism; history of convulsive disorders; history of head injury)
• Current use of stimulants, opioids, benzodiazepines or other Central Nervous System (CNS) depressant
• Positive toxicology screen for opioids, stimulants, or recreational drugs
• Pregnancy or lactation
• Significant preadmission psychological distress.

Healthy Control and CLBP-Specific Exclusion Criteria:

• Report current medical/psychiatry history
• Report acute painful injury (within 3 months)
• Have a diagnosed chronic pain disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uninterrupted Sleep; Participants will be permitted to sleep without interruption for 8 hours.	Drug: Within-Subject test of blinded study medication; On the day after each sleep condition (Uninterrupted Sleep and Sleep Disruption), participants will undergo multiple injections of study medication or placebo. This is a double-blind within-subject Phase II trial. As such, study medications must remain blinded. Participants may receive a medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications, or placebo (saline). This study uses a within-subject design, such that participants serve as participants' own control.
Experimental: Sleep Disruption; Participants will be repeatedly awakened throughout the night according to a standardized protocol.	Drug: Within-Subject test of blinded study medication; On the day after each sleep condition (Uninterrupted Sleep and Sleep Disruption), participants will undergo multiple injections of study medication or placebo. This is a double-blind within-subject Phase II trial. As such, study medications must remain blinded. Participants may receive a medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications, or placebo (saline). This study uses a within-subject design, such that participants serve as participants' own control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Liking as assessed by the Visual Analog Scale	Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Do you like the drug?"	up to 420 minute post-medication administration
Heat Pain Threshold	A thermode will gradually increase in temperature until the participant indicates when it "first feels painful". The outcome will be the temperature (degrees Celsius) at which the participant indicates they first feel pain.	up to 420 minute post-medication administration
Suprathreshold Tonic Heat Pain	A painful temperature above threshold will be held tonically for a period of time, after which pain ratings are obtained on a 0-100 numerical rating scale, where 0 = "No Pain" and 100 = "Worst Pain Imaginable."	up to 420 minute post-medication administration
Monetary Valuation of Drug as assessed by the Drug vs. Money Multiple Choice Questionnaire	Participants are presented with an array of choices (in dollar value) which they will compare to the option of receiving study drug. They will decide for each choice whether they would take the money (at that value) or the drug they received in the session. The outcome will be the "crossover point", which is the mean of the last price that the participant selected "drug" and the first price at which the participant selected "money".	up to 420 minute post-medication administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Good Drug Effects as assessed by the Visual Analog Scale	Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does the drug have any good effects?"	up to 420 minute post-medication administration
Bad Drug Effects as assessed by the Visual Analog Scale	Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does the drug have any bad effects?"	up to 420 minute post-medication administration
Level of "Highness" as assessed by Visual Analog Scale	Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "How high are you?"	up to 420 minute post-medication administration
Feeling of Sickness as assessed by Visual Analog Scale	Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does this drug make you feel sick?"	up to 420 minute post-medication administration
Clinical Pain	This will be rated on a 0-100 Numerical Rating Scale, where 0 = "No Pain" and 100 = "Worst Pain Imaginable."	up to 420 minute post-medication administration

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Michael T. Smith, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Estimated): April 29, 2025
• Study Completion (Estimated): April 29, 2025

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: IRB00160629; R01DA048206 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No