Patient-Oriented Clinical Research

old_manUntil PiPS researchers began contributing to the field of placebo studies, there had been comparatively little patient-centered research aimed at harnessing placebo responses in the treatment of common illnesses. PiPS has addressed this gap by creating a comprehensive agenda for placebo research that targets high-priority clinical challenges.

Taking advantage of the research-intensive environment and clinical resources at Harvard University and its teaching hospitals, the PiPS team has completed or is in the process of completing clinical studies related to the following illnesses. The majority of these studies were funded by grants from the National Institutes of Health (NIH).

  • Asthma

    In an article published by the New England Journal of Medicine in July 2011, the PiPS team demonstrated the impact of placebos on subjective outcomes: placebos can have effects similar to powerful medications as measured by a self-appraisal of subjective symptoms, yet have no detectable effect on objective pathophysiology. This study was funded by NCCIH (formerly NCCAM), NIH.

  • Irritable bowel syndrome (IBS)

    In an article published in PLoS in 2010, the PiPS team reported an RCT that suggested that when patients were informed about the potential for benefit from the placebo response, deception was not required to produce benefit from placebo treatment (described as a pill without any medication in it). The study established the “proof-of-concept” that it may be possible to directly harness placebo effects while still conforming to ethical norms of informed consent. PiPS plans to extend this investigation to other clinical conditions with the goal of further elucidating how to optimize the use of placebo treatments in patient care.

    In a related study published by the British Medical Journal in 2008, PiPS researchers showed that placebo treatment for IBS could be administered in a dose dependent manner analogous to drug administration. They also demonstrated that components of the therapeutic encounter such as empathy, confidence, thoughtful silence and touch could dramatically improve clinical outcomes. Both of these studies were funded by NCCIH (formerly NCCAM), NIDDK, NIH.

  • Chronic arm pain

    In a clinical trial, the PiPS team demonstrated that placebo needles produce better pain relief than placebo pills but that placebo pills are better for insomnia. These findings suggest the complex symbolic nature of the placebo response. This study was funded by NCCIH (formerly NCCAM), NIH.

  • Acute migraine headache

    PiPS researchers have carried out a methodological study to develop ways to 1) treat patients more effectively and 2) more efficiently distinguish between the effects of medication and placebo treatment. The results of this work have the potential to improve drug development for migraine headaches and produce methodologies that will be useful in examining the role of placebo treatments in other illnesses.

  • Depression

    In a series of influential meta-analyses, PiPS researchers documented the exceptionally high rate of placebo response in depression. The team recently began a pilot study examining how to maximize placebo effects in the clinical care of depression. In a widely cited methodological article, PiPS researchers also elucidated statistical practices that can produce distorted perceptions of clinical efficacy. This study is partly funded by NCCIH (formerly NCCAM), NIH.

  • Osteoarthritis of the Knee

    Using clinical research methodologies and functional magnetic resonance imaging, PiPS researchers are currently investigating how expectations modulate responses to sham acupuncture and genuine acupuncture. This study is being funded by NCCIH (formerly NCCAM), NIH.

  • Chronic Low Back Pain

    Using positron emission tomography (PET) embedded in a clinical trial, the PiPS team is currently conducting a major study that examines how expectations and the patient-provider relationship can modulate the treatment of low back pain as measured by clinical outcomes, neural circuitry involvement and modulation of neurotransmitter systems. This study is being funded by NCCIH (formerly NCCAM), NIH.

In the future, PiPS plans to investigate the effects of placebos in Parkinson’s disease, heart disease, hypertension, benign prostatic hyperplasia and the management of cancer symptoms. In these endeavors, we aim to determine whether the ritual of treatment, including the patient-provider relationship, can be ethically used to produce a positive effect on clinical outcomes.

Related publications:

Nurko S, Saps M, Kossowsky J, Zion SR, DiLorenzo C, Vaz K, Hawthorne K, Wu R, Ciciora S, Rosen JM, Kaptchuk TJ, Kelley JM. Effect of open-label placebo on children and adolescents with functional abdominal pain or irritable bowel syndrome: A randomized clinical trial.  JAMA Pediatrics 2022

Flowers K, Patton M, Hruschak V, Fields K, Schwartz E, Zeballos J, Kang J, Edwards R, Kaptchuk TJ, Schreiber K.  Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial. PAIN 2021

Lembo A, Kelley J, Nee J, Iturrino J, Chang V, Rangan V, Katon J, Hirsch W, Kirsch I, Hall K, Davis R, Kaptchuk TJ.  Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial.  PAIN 2021

Carvalho C, Pais M, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo for chronic low back pain: a 5-year follow-up PAIN 2021

Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci. Transl. Med. 6, 218ra5 (2014)

Kelley JM, Kaptchuk TJ, Cusin C, Lipkin S, Fava M. Open-label placebo for Major Depressive Disorder: a pilot ramdomized controlled trial. Psychother Psychosom 2012;81:312-314

Weschler M et al. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med. 2011 Jul 14;365(2):119-26.

Kaptchuk TJ et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One 2010; 5: e15591.

Kaptchuk TJ et al. Components of the placebo effect: a randomized controlled trial in irritable bowel syndrome. BMJ 2008; 336: 998-1003.

Kirsch I et al. Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine 2008; 5(2).

Kirsch I, Moncrieff J. Clinical trials and the response rate illusion. Contemporary Clinical Trials 2007: 28 (4), 348-351.

Kaptchuk TJ et al. Sham device versus inert pill: a randomized controlled trial comparing two placebo treatments for arm pain due to repetitive strain injury. BMJ 2006; 332: 291-7.

Kirsch I et al. The emperor’s new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention and Treatment 2002; 5(23).

Kirsch I, Sapirstein G. Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention and Treatment 1998; 1 (Article 0002a).



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