Sleep Disruption's Impact on Medication Efficacy for Lower Back Pain

Overseen By Michael T. Smith, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Stimulants, Opioids, Benzodiazepines, others

Disqualifiers: Bipolar, Seizure, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 nights

250 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not currently use stimulants, opioids, benzodiazepines, or other Central Nervous System (CNS) depressants. If you are taking any of these, you would need to stop before participating.

What data supports the effectiveness of this treatment for sleep disruption's impact on medication efficacy for lower back pain?

Research shows that sleep problems can worsen recovery and increase pain intensity in people with chronic low back pain. Addressing sleep issues may improve outcomes, suggesting that treatments targeting sleep could be beneficial. ^{1 2 3 4 5}

Is the treatment for sleep disruption in low back pain safe for humans?

A study on a combination of naproxen sodium and diphenhydramine for low back pain with sleep issues suggests it is safe, but more research is needed to confirm this for different treatments. ^{1 2 3 6 7}

How does the treatment for sleep disruption impact medication efficacy for lower back pain?

This treatment is unique because it focuses on how sleep disruption affects the effectiveness of medications for lower back pain, which is not commonly addressed in other treatments. It highlights the importance of sleep quality in managing pain, suggesting that improving sleep could enhance the overall treatment outcomes for lower back pain. ^{2 3 5 8 9}

What is the purpose of this trial?

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.

Research Team

Michael T. Smith, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-60, both healthy and those with chronic low back pain (CLBP), who consume less than two caffeinated drinks daily. Participants must not be pregnant or breastfeeding, have significant psychological distress, a recent painful injury, other chronic pain disorders, severe medical conditions, or a history of opioid use disorder.

Inclusion Criteria

You drink less than 2 servings of caffeinated drinks per day and are willing to stop drinking them for 3 days before the study.

You drink less than 2 servings of caffeinated drinks each day and are willing to stop drinking them for 3 days before the study starts.

I have chronic low back pain.

Exclusion Criteria

You have abnormal results on blood and metabolic tests that are important for your health.

I do not have severe asthma, lung, liver, kidney problems, thyroid issues, adrenal gland issues, stomach blockage, gallbladder disease, severe alcoholism, a history of seizures or head injuries.

You are experiencing significant emotional distress before joining the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a randomized crossover experiment with placebo-controlled effects of study medication on abuse liability metrics and response to pain measures after one night of uninterrupted sleep and one night of sleep disruption.

2 nights

2 visits (in-person)

Follow-up

Participants are monitored for subjective responses to medication and pain testing after treatment

1 week

Treatment Details

Interventions

• Effects of Sleep Disruption

Trial Overview The study tests how sleep disruption affects responses to medication in terms of potential abuse and pain relief. It's a mixed between-within randomized crossover experiment comparing the effects after normal sleep versus disrupted sleep on drug liking and valuation as well as response to standardized pain measures.

Participant Groups

Group I: Sleep Disruption Experimental Treatment 1 Intervention

Participants will be repeatedly awakened throughout the night according to a standardized protocol.

Group II: Uninterrupted Sleep Active Control 1 Intervention

Participants will be permitted to sleep without interruption for 8 hours.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study of 761 chronic low back pain patients, those who reported sleep problems at the start were significantly more likely to experience nonrecovery (odds ratio 1.52) and higher pain intensity (odds ratio 2.69) after 6 months.

Patients who developed sleep problems over time had even greater odds of nonrecovery (odds ratio 2.17) and increased pain intensity (odds ratio 2.95), highlighting the importance of addressing sleep issues in treatment plans for low back pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent and Developing Sleep Problems: A Prospective Cohort Study on the Relationship to Poor Outcome in Patients Attending a Pain Clinic with Chronic Low Back Pain. Pakpour, AH., Yaghoubidoust, M., Campbell, P.[2022]

Out of 282 trials on chronic low back pain published between 2010 and 2022, only 9.2% included any sleep measures, indicating a significant gap in understanding how sleep affects pain treatment outcomes.

Only 4.6% of the trials collected formal sleep disturbance measures at multiple time points, highlighting the need for better adherence to guidelines that recommend capturing sleep quality to enhance insights into the relationship between sleep and chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measures of sleep disturbance are not routinely captured in trials for chronic low back pain: a systematic scoping review of 282 trials. Neilson, BD., Dickerson, C., Young, JL., et al.[2023]

In a study of 268 patients with chronic low back pain, there was a significant relationship between pain levels and sleep disturbances, with a 55% increase in reports of restless or light sleep after pain onset.

The study found that sleep quality was notably poor among patients using orthopedic mattresses, highlighting the need to address sleep issues as part of managing chronic pain effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep disturbance in patients with chronic low back pain. Marin, R., Cyhan, T., Miklos, W.[2022]

In a study of 482 patients with back pain, 213 reported experiencing night pain, but no serious spinal pathology was found in these cases, suggesting that night pain may not be a reliable indicator of serious conditions.

Patients with night pain experienced significant sleep disruption and higher levels of disability and anxiety, indicating that while night pain is a distressing symptom, it may not necessarily correlate with severe underlying issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The symptom of night pain in a back pain triage clinic. Harding, IJ., Davies, E., Buchanan, E., et al.[2019]

In a study of 6200 participants from the Norwegian HUNT study, individuals experiencing sleeplessness had a significantly lower probability of recovering from chronic low back pain (LBP), with recovery rates of 0.65 for women and 0.81 for men compared to those without sleep issues.

For those with chronic LBP who also reported multiple pain sites, the recovery probability was even lower, with rates dropping to 0.40 for women and 0.59 for men, highlighting the importance of addressing sleep problems to improve recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of sleep problems and co-occurring musculoskeletal pain on long-term prognosis of chronic low back pain: the HUNT Study. Skarpsno, ES., Mork, PJ., Nilsen, TIL., et al.[2020]

The combination of naproxen sodium 440 mg and diphenhydramine 50 mg significantly improved wake time after sleep onset (WASO) compared to naproxen sodium 550 mg, indicating better sleep maintenance in subjects with low back pain and transient insomnia.

This combination also resulted in a greater reduction in average pain intensity compared to both naproxen sodium 550 mg and paracetamol 1000 mg/diphenhydramine 50 mg, while being well tolerated with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial]. Barantsevich, ER., Karakulova, YV., Baranova, NS., et al.[2022]

A randomized controlled trial involving 60 participants with chronic low back pain showed that most had sleep disturbances, indicating a strong need for effective interventions.

All treatment groups (walking program, supervised exercise, and usual physiotherapy) reported improvements in sleep quality over 3 and 6 months, suggesting that physiotherapy may be beneficial for addressing sleep issues in chronic low back pain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiotherapy for sleep disturbance in people with chronic low back pain: results of a feasibility randomized controlled trial. Eadie, J., van de Water, AT., Lonsdale, C., et al.[2022]

Improvements in self-reported sleep quality and total sleep time are significantly correlated with reductions in chronic low back pain (CLBP), based on moderate-quality evidence from a systematic review of 6 studies involving 1641 participants.

The review found low-quality evidence suggesting that better sleep quality may also lead to improvements in CLBP-related disability, but the relationship between baseline sleep quality and future pain/disability remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are Changes in Sleep Quality/Quantity or Baseline Sleep Parameters Related to Changes in Clinical Outcomes in Patients With Nonspecific Chronic Low Back Pain?: A Systematic Review. Chang, JR., Wang, X., Lin, G., et al.[2023]

In a study of 409 patients with non-specific neck and/or back pain, those who reported good sleep at the start were more likely to see significant improvements in pain and disability after one year.

Specifically, good sleep was associated with over twice the odds of achieving meaningful pain relief and nearly twice the odds of reduced disability, highlighting the importance of sleep quality in managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal pain--good sleep matters: a secondary analysis of a randomized controlled trial. Paanalahti, K., Wertli, MM., Held, U., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Persistent and Developing Sleep Problems: A Prospective Cohort Study on the Relationship to Poor Outcome in Patients Attending a Pain Clinic with Chronic Low Back Pain. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Measures of sleep disturbance are not routinely captured in trials for chronic low back pain: a systematic scoping review of 282 trials. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Sleep disturbance in patients with chronic low back pain. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The symptom of night pain in a back pain triage clinic. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Influence of sleep problems and co-occurring musculoskeletal pain on long-term prognosis of chronic low back pain: the HUNT Study. [2020]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial]. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Physiotherapy for sleep disturbance in people with chronic low back pain: results of a feasibility randomized controlled trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Are Changes in Sleep Quality/Quantity or Baseline Sleep Parameters Related to Changes in Clinical Outcomes in Patients With Nonspecific Chronic Low Back Pain?: A Systematic Review. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Spinal pain--good sleep matters: a secondary analysis of a randomized controlled trial. [2018]