Placebo for Cancer-Related Fatigue

Overseen By Sriram Yennu

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Surgery, Substance abuse, Cognitive impairment

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: Unknown

Duration: 4 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II/III trial studies an open labeled placebo to see how well it works compared with waitlist control in reducing cancer related fatigue in patients with cancer that has spread to other places in the body. A placebo is not a drug and is not designed to treat any disease or illness. Recent studies have found that cancer related fatigue symptoms in cancer survivors are improved with open labeled placebo (that is, patients know they are taking a placebo). It is not yet known how well an open labeled placebo works when compared with waitlist control in reducing cancer related fatigue.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on opioids for cancer pain, you must not have had a major dose change in the 48 hours before starting the study.

What data supports the effectiveness of the treatment Open Labeled Placebo for cancer-related fatigue?

Research shows that open-label placebo (OLP) can reduce fatigue in cancer survivors, as demonstrated in a randomized trial where OLP improved symptoms of cancer-related fatigue. ^{1 2 3 4 5}

Is open-label placebo safe for humans?

Open-label placebo (OLP) has been studied in various conditions and is generally considered safe for humans, as it involves taking an inactive substance with no active drug ingredients. ^{1 3 4 6 7}

How does the open-label placebo treatment for cancer-related fatigue differ from other treatments?

The open-label placebo treatment for cancer-related fatigue is unique because it involves patients knowingly taking a placebo, which has been shown to improve symptoms in other conditions. Unlike other treatments that may involve drugs or therapies like exercise or cognitive-behavioral therapy, this approach relies on the psychological and biological effects of taking a placebo openly. ^{1 3 4 5 7}

Research Team

Sriram Yennu

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced cancer experiencing fatigue for at least two weeks. They must have a hemoglobin level of >= 8 g/dL, stable pain management if on opioids, and be able to engage in telephone follow-ups. Excluded are those with recent surgery, substance abuse issues, or significant cognitive impairment.

Inclusion Criteria

My hemoglobin level is at least 8 g/dL, possibly after a transfusion.

I am 18 years old or older.

Exclusion Criteria

I have not had surgery or pain relief procedures within the last 2 weeks.

Patients with history of substance abuse (Cut down, Annoyed, Guilty, Eye opener [CAGE] >= 2+), cognitively impaired (MD Anderson Symptom [MDAS] > 7)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive open labeled placebo orally twice daily for 4 weeks in the absence of disease progression

4 weeks

Weekly visits (in-person or virtual)

Waitlist Control

Participants are assigned to a waiting list during week 1, then receive open labeled placebo orally twice daily for 3 weeks

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Open Labeled Placebo

Trial Overview The study compares the effects of an openly labeled placebo (patients know they're taking a placebo) against a waitlist control group to see which reduces cancer-related fatigue better in patients with advanced cancer.

Participant Groups

Group I: Arm I (open labeled placebo) Experimental Treatment 3 Interventions

Patients receive open labeled placebo PO BID for 4 weeks in the absence of disease progression.

Group II: Arm II (waiting list, open labeled placebo) Active Control 4 Interventions

Patients are assigned to a waiting list during week 1. Beginning in week 2, patients receive open labeled placebo PO BID for 3 weeks in the absence of disease progression.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A systematic review of 30 randomized controlled trials involving cancer-related fatigue (CRF) found a statistically significant placebo response, with a pooled standardized mean change of -0.23, indicating that patients in the placebo groups experienced a notable reduction in fatigue.

The study highlights the need for researchers to consider alternative trial designs in future CRF drug studies to better account for the placebo response, as all included trials had limitations that increased their risk of bias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression. Roji, R., Stone, P., Ricciardi, F., et al.[2022]

In a study involving 84 patients with advanced cancer, an open-labeled placebo (OLP) significantly reduced cancer-related fatigue (CRF) after one week compared to a waitlist control, with a mean improvement of 6.6 points on the FACIT-F scale versus 2.1 points for the control group.

The benefits of the OLP were sustained for four weeks after the initial treatment, indicating its potential efficacy in managing fatigue in advanced cancer patients, with no significant adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo for the Treatment of Cancer-Related Fatigue in Patients with Advanced Cancer: A Randomized Controlled Trial. Yennurajalingam, S., Azhar, A., Lu, Z., et al.[2023]

In a study of 40 cancer survivors, those receiving open-label placebo (OLP) reported significant improvements in cancer-related fatigue (CRF) after 3 weeks, indicating that even when participants know they are taking a placebo, it can still be effective.

The improvement in CRF was influenced by genetic factors related to dopamine metabolism, suggesting that individual biological differences may play a role in how well placebos work for symptom management in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label placebo reduces fatigue in cancer survivors: a randomized trial. Zhou, ES., Hall, KT., Michaud, AL., et al.[2020]

In a small study of 27 cancer patients undergoing radiation therapy, both true and sham acupuncture showed improvements in fatigue and quality of life, but the differences were not statistically significant, indicating that more research is needed to confirm these findings.

The true acupuncture group showed a greater improvement in fatigue scores compared to the sham group, suggesting potential benefits of acupuncture, but the study was underpowered, indicating that a larger trial with at least 75 subjects per group is necessary to draw more definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue. Balk, J., Day, R., Rosenzweig, M., et al.[2022]

In a study of 105 patients with cancer-related fatigue, 56% showed a significant placebo response, indicating that many patients can experience improvements in fatigue even when receiving a placebo treatment.

Worse baseline physical well-being, particularly in areas like anxiety and sleep, was linked to a higher likelihood of experiencing a placebo response, suggesting that patient characteristics should be carefully considered in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer. de la Cruz, M., Hui, D., Parsons, HA., et al.[2021]

Cancer-related fatigue (CRF) affects 43.0% of cancer patients, with a total prevalence of 70.7% when including mild fatigue, highlighting its significant impact on patient well-being and treatment compliance.

The study found that severe CRF prevalence varies by cancer type and treatment phase, with chemotherapy leading to a higher prevalence (33.1%) compared to surgery (22.0%) and radiotherapy (24.2%), and female patients experiencing 1.4 times more severe fatigue than males.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis. Kang, YE., Yoon, JH., Park, NH., et al.[2023]

Cancer-related fatigue (CRF) is a common and distressing symptom experienced by cancer patients throughout their journey, yet it is often underdiagnosed and poorly managed.

Evidence from controlled trials indicates that interventions like exercise, psycho-educational programs, and cognitive-behavioral therapy for insomnia are effective in treating CRF, highlighting the need for more rigorous studies to identify the best treatments for specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer-related fatigue: state of the science. Mitchell, SA.[2010]

References

1. England pubmed.ncbi.nlm.nih.gov

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Open-Label Placebo for the Treatment of Cancer-Related Fatigue in Patients with Advanced Cancer: A Randomized Controlled Trial. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Open-label placebo reduces fatigue in cancer survivors: a randomized trial. [2020]

4. Canada pubmed.ncbi.nlm.nih.gov

Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue. [2022]

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

Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer. [2021]

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

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis. [2023]

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

Cancer-related fatigue: state of the science. [2010]