Multiple Treatments for Chronic Pain

(CPMP Trial)

Recruiting at40 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Eli Lilly and Company

Disqualifiers: Heart block, Cancer, Fibromyalgia, Substance use, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing different treatments for chronic pain in patients with knee osteoarthritis, chronic low back pain, and diabetic nerve pain. It aims to find effective ways to reduce their chronic pain.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all medications for chronic pain, except for rescue medication, during the study.

What data supports the effectiveness of the drug LY3016859 ISA and similar treatments for chronic pain?

Research shows that placebo treatments can significantly reduce pain in individuals with chronic pain conditions, such as osteoarthritis and fibromyalgia, similar to healthy individuals. This suggests that the placebo effect, which can be enhanced by giving patients control over treatment administration, may improve pain outcomes. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The research articles do not provide specific safety data for the treatments listed under different names, but they do mention that in trials for fibromyalgia, some drugs had adverse effects leading to drop-outs. This suggests that while some treatments may be generally safe, they can still cause side effects in some people. ^{6 7 8 9 10}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for adults with chronic pain from conditions like osteoarthritis or diabetic neuropathy, who've had daily pain for at least 12 weeks. Participants must be willing to stop all other pain meds except emergency ones, not start new therapies during the study, have a BMI under 40 kg/m², and score specific values on pain scales.

Inclusion Criteria

Your pain level, as measured on a scale, falls between 40 and 95.

Your body mass index is less than 40 kg/m².

Your score on the pain catastrophizing scale is 30 or lower.

Exclusion Criteria

You have had a problem with alcohol, illegal drugs, or pain medicines in the past 2 years.

I have not had any cancer except for skin cancer that was removed, in the last 2 years.

I have a serious heart rhythm problem.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either active intervention or matching placebo for chronic pain conditions

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LY3016859 ISA (Other)
• LY3526318 ISA (Other)
• LY3556050 ISA (Other)
• LY3857210 ISA (Other)
• Placebo (Other)
• Placebo Oral (Other)

Trial Overview The study tests multiple interventions (LY3857210 ISA, LY3526318 ISA, etc.) against placebos to manage chronic pain. It's designed to allow each intervention-specific appendix (ISA) to begin independently as they become ready for clinical trials within an overarching protocol.

Participant Groups

Group I: LY3857210 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group II: LY3857210 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group III: LY3857210 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group IV: LY3556050 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group V: LY3556050 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group VI: LY3556050 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group VII: LY3526318 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group VIII: LY3526318 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group IX: LY3526318 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group X: LY3016859 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Group XI: LY3016859 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Group XII: LY3016859 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

In a study involving 87 healthy volunteers, providing individuals with control over when they administer a placebo treatment significantly enhanced the effectiveness and duration of placebo analgesia compared to standard passive conditioning.

Participants with instrumental control not only experienced greater pain relief but also showed reduced anxiety responses, suggesting that giving patients control could be a simple and ethical way to improve pain management outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instrumental Control Enhances Placebo Analgesia. Tang, B., Geers, A., Barnes, K., et al.[2020]

In a study involving 237 participants (60 with osteoarthritis, 79 with fibromyalgia, and 98 healthy individuals), those with chronic pain experienced a significant reduction in pain from a placebo treatment, similar to healthy individuals.

The study found that the magnitude of placebo analgesia and the expectation of pain relief were comparable across all diagnostic groups, suggesting that individuals with chronic pain can effectively respond to placebo treatments despite their psychological challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. Power, A., Brown, CA., Sivan, M., et al.[2022]

In a study involving 52 Japanese patients with chronic low back pain, the addition of open-label placebo (OLP) to standard treatment did not show superior benefits compared to standard treatment alone after 3 and 12 weeks.

Both groups experienced significant improvements in functional disability, indicating that while OLP did not enhance outcomes, standard treatment was effective in reducing disability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain. Ikemoto, T., Ueno, T., Arai, YC., et al.[2021]

In a review of 42 trials on neuropathic pain and 29 trials on low back pain, it was found that participants on placebo consumed significantly more rescue medication (RM) than those on active drugs, which could mask the true effectiveness of the treatments.

Specifically, in trials showing a small to medium effect size for the investigational drugs, placebo participants used 17% to 30% more RM, highlighting the need for better analytical methods to account for RM consumption in chronic pain studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of rescue medication in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain. Grøvle, L., Hasvik, E., Haugen, AJ.[2023]

Nabiximols demonstrated a significant reduction in chronic neuropathic pain compared to placebo, with a mean difference of -0.40 on a pain scale, based on a systematic review of nine randomized controlled trials involving 1289 participants.

The evidence quality was moderate, indicating that while nabiximols showed a small but meaningful effect, further larger studies are needed to confirm its efficacy in treating neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials. Dykukha, I., Malessa, R., Essner, U., et al.[2021]

In a study involving knee osteoarthritis and non-radicular low back pain patients, significant placebo effects were observed, particularly in pain intensity and range of motion, indicating that the placebo response can influence both self-reported and performance-based outcomes.

The study found that gender and diagnosis affected the magnitude of placebo responses, with women in the knee osteoarthritis group showing notable improvements, suggesting that these factors should be considered in future clinical trials to better understand and potentially mitigate placebo effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Managing" the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models. Harden, RN., Saracoglu, M., Connolly, S., et al.[2018]

In a review of 18 studies involving 3546 patients with fibromyalgia syndrome, a significant 18.6% of participants experienced a 50% reduction in pain from placebo treatments, highlighting the strong placebo effect in chronic pain trials.

The study also found that 10.9% of patients in placebo groups dropped out due to adverse events, indicating a notable nocebo effect, which suggests that both placebo and nocebo responses play a critical role in the perceived efficacy and safety of drug treatments for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. Häuser, W., Sarzi-Puttini, P., Tölle, TR., et al.[2022]

A systematic review of 108 randomized placebo-controlled trials involving 44,171 participants found that using an enriched study design did not significantly change the treatment effect size for pain intensity in chronic musculoskeletal pain.

However, enriched designs were associated with a reduced risk of adverse events for opioid treatments, suggesting they may enhance safety in certain analgesic trials, although this effect was not observed for other analgesics or serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effect sizes between enriched and nonenriched trials of analgesics for chronic musculoskeletal pain: a systematic review. Yamato, TP., Maher, CG., Saragiotto, BT., et al.[2021]

In a study of 884 patients with fibromyalgia, milnacipran at a dose of 200 mg/day significantly improved pain and overall symptoms compared to placebo, demonstrating its efficacy in treating fibromyalgia.

Milnacipran was found to be safe and well tolerated, with common side effects including nausea, hyperhidrosis, and headache, indicating it can be a viable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. Branco, JC., Zachrisson, O., Perrot, S., et al.[2022]

References

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

Instrumental Control Enhances Placebo Analgesia. [2020]

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

Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. [2022]

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

Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain. [2021]

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

Impact of rescue medication in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain. [2023]

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

Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

"Managing" the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Newer treatments for fibromyalgia syndrome. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of effect sizes between enriched and nonenriched trials of analgesics for chronic musculoskeletal pain: a systematic review. [2021]

10. Canada pubmed.ncbi.nlm.nih.gov

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. [2022]