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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how sleep disruption affects medication effectiveness for individuals with chronic low back pain. Researchers aim to determine if interrupted sleep alters patients' perceptions of their medication and their pain response. The study compares nights of normal sleep with nights of repeated disturbances. It seeks participants diagnosed with chronic low back pain who experience ongoing discomfort. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that people with lower back pain often wake up multiple times during the night, and many with chronic back pain also experience sleep difficulties. However, the link between sleep problems and back pain remains weak, so not everyone with back pain will have sleep issues, and not everyone with sleep issues will have back pain.

Regarding safety, this study is in an early phase, meaning researchers are still assessing how well the treatment is tolerated. So far, there is little evidence of serious side effects directly related to sleep disruption in similar studies. However, sleep disruption can sometimes cause fatigue or irritability. This research is designed to carefully monitor participants to ensure their safety as much as possible. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how sleep interruption might affect the effectiveness of medication for lower back pain. While typical treatments focus on medications like NSAIDs or muscle relaxants, this study examines a new angle: the role of sleep quality. By comparing uninterrupted sleep with sleep disruption, researchers aim to uncover how sleep patterns could influence pain relief. This could lead to a deeper understanding of integrating sleep management with existing treatments, potentially enhancing their effectiveness.

What evidence suggests that sleep disruption affects medication efficacy for lower back pain?

This trial will compare the effects of uninterrupted sleep with sleep disruption on medication efficacy for lower back pain. Research has shown that sleep quality significantly impacts the effectiveness of pain treatments. Studies have found that people with chronic low back pain who sleep better may experience more effective medication results. Opioids, commonly used for pain relief, can also enhance sleep and alleviate sleep issues. Disturbed sleep might reduce the effectiveness of these medications in relieving pain. Therefore, improving sleep could be crucial for successfully managing chronic low back pain. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael T. Smith, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

You are experiencing significant emotional distress before joining the trial.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1087079222000855

The short-term effects of opioid and non ... In summary, this review shows that opioid interventions improve sleep quality and reduce sleep disturbance in people with chronic LBP. Caution should be taken ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5082544/

Sleep disturbance in patients taking opioid medication for ... This study investigated activity and sleep patterns in patients taking opioid and non‐opioid analgesia for chronic back pain.

3. withpower.com withpower.com/trial/phase-3-low-back-pain-9-2019-14e3b

Sleep Disruption's Impact on Medication Efficacy for Lower ... It highlights the importance of sleep quality in managing pain, suggesting that improving sleep could enhance the overall treatment outcomes for lower back pain ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2518999/

Quality of sleep in patients with chronic low back pain This study was conducted to evaluate if sleep disorders and chronic pain associated are more frequently than one would expect.

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00478-3/fulltext

Effects of pharmacotherapy on sleep-related outcomes in ... Recent evidence in adults with CLBP indicated that opioid therapies improved sleep quality and reduced sleep disturbance, although an estimate ...

6. journals.lww.com journals.lww.com/spinejournal/fulltext/2025/01010/association_between_sleep_disturbance_and_low_back.14.aspx

Association Between Sleep Disturbance and Low Back Pain The purpose of the report published in Spine 2022 1 was to assess the effect of sleep disturbance on low back pain, especially focusing on the duration and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9830709/

Sleep Disturbance in Musculoskeletal Conditions: Impact ... Patients reporting comorbid sleep disturbance had significant improvement in sleep, alongside pain, mental health and work productivity at ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3082679/

Prevalence of sleep disturbance in patients with low back ... Our findings indicate that sleep disturbance is common in patients with LBP. In addition, we found that the intensity of back pain was only weakly associated ...

9. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1429495/full

Sleeping <6.55 h per day was associated with a higher risk ... Our findings indicate that shorter sleep duration is a risk factor for LBP in adults aged over 50 years.

10. ajmc.com ajmc.com/view/evidence-linking-sleep-to-improved-lower-back-pain-outcomes-is-weak-more-studies-needed

Evidence Linking Sleep to Improved Lower Back Pain ... The authors point to a systematic review that revealed almost 75% of individuals enduring chronic back pain experience poor quality of sleep ...