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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a placebo, a treatment with no active medicine, can reduce fatigue in individuals with advanced cancer that has spread. Participants will know they are taking an open-label placebo, which has shown promise in alleviating fatigue symptoms in cancer survivors. The trial compares two groups: one receives the placebo immediately, while the other starts a week later. Individuals with advanced cancer who experience significant fatigue lasting at least two weeks and can participate in phone follow-ups might be suitable for the trial. 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 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.

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

Research shows that using an open-labeled placebo, where patients know they are receiving a placebo, can help reduce cancer-related tiredness. Studies have found that this method can lessen fatigue in patients with advanced cancer in just one week. Because a placebo is not a real drug, it lacks the side effects that medicines usually have, making it very safe for patients. Past trials indicate that patients have handled open-labeled placebos well, with no major negative effects reported. Overall, this suggests that the treatment is safe for those dealing with cancer-related fatigue. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using an open-labeled placebo for cancer-related fatigue because it explores the power of the mind-body connection in a new way. Unlike typical treatments for fatigue, which often involve medications like stimulants or antidepressants, this approach relies on the placebo effect itself. By openly acknowledging that the treatment is a placebo, researchers aim to harness the psychological benefits without deception. This could potentially offer a side-effect-free option, providing relief through the body's natural response to the expectation of treatment.

What evidence suggests that an open labeled placebo is effective for cancer-related fatigue?

Research shows that open-labeled placebos can reduce tiredness in people with advanced cancer. Studies have found that patients felt less tired and experienced a better quality of life after just one week of taking an open-labeled placebo. Even when people know they are taking a placebo—a treatment with no active medicine—they still report feeling less tired. This effect might involve the body's natural ability to feel better, possibly engaging brain systems related to reward and motivation. Although the exact mechanism remains unclear, evidence suggests that open-labeled placebos can ease tiredness in cancer survivors. Participants in this trial will receive an open-labeled placebo, either immediately or after a waiting period, to further explore its effects on cancer-related fatigue. ^{1 2 3 6 7}

Who Is on the Research Team?

Sriram Yennu

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9732231/

Open-Label Placebo for the Treatment of Cancer-Related ... Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.12006

Open-labeled placebo for the treatment of cancer-related- ... Open labeled placebo was efficacious in reducing CRF, fatigue cluster, and QOL in fatigued advanced cancer patients at the end of one week.

3. nature.com nature.com/articles/s41598-018-20993-y

Open-Label Placebo Treatment for Cancer-Related Fatigue OLP may reduce fatigue symptom severity and fatigue-related quality of life disruption in cancer survivors. Similar content being viewed by ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36106759/

Open-Label Placebo for the Treatment of Cancer ... - PubMed Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week.

5. programinplacebostudies.org programinplacebostudies.org/wp-content/uploads/2018/10/Zhou2018_Article_Open-labelPlaceboReducesFatigu.pdf

Open-label placebo reduces fatigue in cancer survivors Conclusions Results demonstrate that even when administered openly, placebos improve CRF in cancer survivors and dopami- nergic systems may be associated with ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S088539242500716X

Improvement of Fatigue Due to Placebo in Blinded and ... In this study we found placebo response was not significantly different between patients receiving placebo in a blinded and open-labeled design in randomized ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02522988

The Use of an Open Label Placebo to Treat Cancer ... The purpose of this randomized-controlled, crossover pilot trial is to evaluate the feasibility, acceptability and effects of a non-deceptive (open-label) ...