Does Placebo Information Affect the Trial Outcomes and Participant Blinding?

Effect of Information on Placebo in the Informed Consent on the Trial Outcomes and Participant Blinding

This is a randomised sham-controlled trial involving healthy volunteers to determine the effect of information on placebo, i.e., sham acupuncture, given in the informed consent, on the trial outcomes and blinding status of participants in a trial.

Study Overview

• Status: Completed
• Conditions: Muscle Soreness
• Intervention / Treatment: Device: acupuncture; Device: Park Sham Needle

Detailed Description

A total of 89 healthy volunteers will be recruited and randomly allocated to one of the 4 groups at an identical ratio. Four groups differ in acupuncture and placebo information. It is summarized as follows:

1. to receive real acupuncture and to read fully disclosed sham acupuncture information (e.g., fake acupuncture) written in the informed consent
2. to receive real acupuncture and to read partially disclosed sham acupuncture information (e.g., different kind of acupuncture) written in the informed consent
3. to receive sham acupuncture (Park Sham Needle) and to read fully disclosed sham acupuncture information written in the informed consent
4. to receive sham acupuncture to read partially disclosed sham acupuncture information (e.g., different kind of acupuncture) written in the informed consent.

They will read informed consent with differently described placebo information following their allocation. After participants repeatedly lift a dumbbell with their non-dominant arm to induce delayed onset muscle soreness (DOMS) in their biceps brachii, they are given allocated acupuncture treatment once a day for three consecutive days including the very first visit to compare outcomes (i.e., relief of DOMS measured with pressure pain threshold and visual analogue scale) and blinding property (the participants will be asked 'which type of acupuncture do you think you have received?' and choose 1 answer out of real, sham, or don't know options).

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 02447
    • Acupuncture & Meridian Science Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age over 18
• not participating in other studies at the time of study participation
• voluntary participation

Exclusion Criteria:

• resistance training for more than 6 months
• experience of fracture of any of four limbs
• pregnancy or breast-feeding at the time of study participation
• analgesics within 24 hours before participation
• any other diseases or conditions that might prevent the participant from receiving acupuncture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: real acupuncture-full disclosure; Participants in this group will be given real acupuncture once a day for three consecutive days including the very first visit and fully disclosed sham acupuncture information in the informed consent (i.e., fake acupuncture).	Device: acupuncture; A sterilised stainless steel needle (diameter 0.25mm X length 40mm, Dongbang Acupuncture Inc., Boryeong, Chungchenongnam-do, Korea) will be given at PC3, LI4, LI11, and LU5 of non-dominant arm for 15 minutes once a day for 3 days (immediately after inducing delayed onset muscle soreness (DOMS), and 2 consecutive days after inducing DOMS).
EXPERIMENTAL: real acupuncture-partial disclosure; Participants in this group will be given real acupuncture once a day for three consecutive days including the very first visit and partially disclosed sham acupuncture information in the informed consent (i.e., different kind of acupuncture).	Device: acupuncture; A sterilised stainless steel needle (diameter 0.25mm X length 40mm, Dongbang Acupuncture Inc., Boryeong, Chungchenongnam-do, Korea) will be given at PC3, LI4, LI11, and LU5 of non-dominant arm for 15 minutes once a day for 3 days (immediately after inducing delayed onset muscle soreness (DOMS), and 2 consecutive days after inducing DOMS).
SHAM_COMPARATOR: sham acupuncture-full disclosure; Participants in this group will be given sham acupuncture once a day for three consecutive days including the very first visit and fully disclosed sham acupuncture information in the informed consent (i.e., fake acupuncture).	Device: Park Sham Needle; A Park Sham Needle (Meridius Medical Ltd. & DongBang Acuprime Ltd., Exeter, UK), non-penetrating sham acupuncture, will be given at two points on the belly of biceps brachii, 1 cun proximedially from LI11, and 1 cun laterally from PC3 of non-dominant arm for 15 minutes once a day for 3 days (immediately after inducing delayed onset muscle soreness (DOMS), and 2 consecutive days after inducing DOMS).; Other Names: sham acupuncture
SHAM_COMPARATOR: sham acupuncture-partial disclosure; Participants in this group will be given sham acupuncture once a day for three consecutive days including the very first visit and partially disclosed sham acupuncture information in the informed consent (i.e., different kind of acupuncture).	Device: Park Sham Needle; A Park Sham Needle (Meridius Medical Ltd. & DongBang Acuprime Ltd., Exeter, UK), non-penetrating sham acupuncture, will be given at two points on the belly of biceps brachii, 1 cun proximedially from LI11, and 1 cun laterally from PC3 of non-dominant arm for 15 minutes once a day for 3 days (immediately after inducing delayed onset muscle soreness (DOMS), and 2 consecutive days after inducing DOMS).; Other Names: sham acupuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change in muscle discomfort from baseline, i.e., immediately after being induced DOMS, measured by visual analogue scale (VAS)	Muscle discomfort of DOMS induced arm is evaluated with VAS ranging from 0 to 10 cm (with 0 indicating no discomfort and 10 experiencing the worst imaginable muscle discomfort.)	day 0; day 1; day 2
Blinding property	Blinding property is evaluated: participants will be asked 'which type of acupuncture do you think you have received?' and choose 1 answer out of experimental group, control group, and do not know. It is calculated following the way of Bang's Blind Index; -1 indicates opposite guessing; 0 indicates random guessing; 1 indicates correct guessing.	day 2
the change in Pressure Pain Threshold (PPT) from baseline, i.e., before being induced DOMS	Pressure Pain Threshold (PPT) will be evaluated on the 5 points of upper non-dominant arm. Five points are selected from 6 equidistance from origin to insertion of biceps brachii with an exception of the first and last point, perpendicular to the belly of the biceps brachii. Pressure was applied to each of these points with increasing force at a rate of approximately 10 N/cm2*sec until the participant reported a painful sensation, and the force value was recorded (N/cm2). An upper limit of PPt was set 50 N/cm2 to avoid bruising.	day 0; day 1; day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acupuncture sensation measured by De-qi questionnaire	De-qi questionnaire (Kim et al.) is used to evaluate acupuncture sensation measured in VAS ranging from 0 to 10 cm (with 0 indicating no feeling of respective 18 items included in the questionnaire and 10 experiencing the worst imaginable feeling of respective 18 items included in the questionnaire.)	day 0; day 1; day 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acupuncture credibility	Credibility of the acupuncture treatment is evaluated using a credibility test by Vincent et al. It is a 4-item self report on a 6-point Likert scale; its score ranges from 4 to 24 point; higher score indicates more credibility over acupuncture.	day 0; day 2
Acupuncture Belief Scale (ABS)	A Korean version of Acupuncture Belief Scale (ABS), a 36-item self-report on a 5-point Likert scale will be used to evaluate acupuncture experiences and beliefs. Its score ranges from 36 to 180 and higher score is considered more positive attitude toward acupuncture.	day 0
State-Trait Anxiety Inventory-X (STAI-X)	A Korean version of State-Trait Anxiety Inventory-X (STAI-X); each item of anxiety has its own 20 different questions on a 4-point Likert scale. The score ranges from 20 to 80, with higher score correlating with greater anxiety.	day 0

Collaborators and Investigators

• Sponsor: Kyunghee University
• Collaborators: University of California, Davis

Publications and helpful links

General Publications

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• Cheon S, Park HJ, Chae Y, Lee H. Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture. BMC Med Res Methodol. 2018 Jan 18;18(1):13. doi: 10.1186/s12874-018-0474-1.
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• Dennehy EB, Webb A, Suppes T. Assessment of beliefs in the effectiveness of acupuncture for treatment of psychiatric symptoms. J Altern Complement Med. 2002 Aug;8(4):421-5. doi: 10.1089/107555302760253612.
• Fleckenstein J, Niederer D, Auerbach K, Bernhorster M, Hubscher M, Vogt L, Banzer W. No Effect of Acupuncture in the Relief of Delayed-Onset Muscle Soreness: Results of a Randomized Controlled Trial. Clin J Sport Med. 2016 Nov;26(6):471-477. doi: 10.1097/JSM.0000000000000259.
• Fleckenstein J, Simon P, Konig M, Vogt L, Banzer W. The pain threshold of high-threshold mechanosensitive receptors subsequent to maximal eccentric exercise is a potential marker in the prediction of DOMS associated impairment. PLoS One. 2017 Oct 6;12(10):e0185463. doi: 10.1371/journal.pone.0185463. eCollection 2017.
• Graves JE, Pollock ML, Leggett SH, Braith RW, Carpenter DM, Bishop LE. Effect of reduced training frequency on muscular strength. Int J Sports Med. 1988 Oct;9(5):316-9. doi: 10.1055/s-2007-1025031.
• Hubscher M, Vogt L, Bernhorster M, Rosenhagen A, Banzer W. Effects of acupuncture on symptoms and muscle function in delayed-onset muscle soreness. J Altern Complement Med. 2008 Oct;14(8):1011-6. doi: 10.1089/acm.2008.0173.
• Lin MJ, Nosaka K, Ho CC, Chen HL, Tseng KW, Ratel S, Chen TC. Influence of Maturation Status on Eccentric Exercise-Induced Muscle Damage and the Repeated Bout Effect in Females. Front Physiol. 2018 Jan 5;8:1118. doi: 10.3389/fphys.2017.01118. eCollection 2017.
• Myers MG, Cairns JA, Singer J. The consent form as a possible cause of side effects. Clin Pharmacol Ther. 1987 Sep;42(3):250-3. doi: 10.1038/clpt.1987.142.
• Shimano T, Kraemer WJ, Spiering BA, Volek JS, Hatfield DL, Silvestre R, Vingren JL, Fragala MS, Maresh CM, Fleck SJ, Newton RU, Spreuwenberg LP, Hakkinen K. Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men. J Strength Cond Res. 2006 Nov;20(4):819-23. doi: 10.1519/R-18195.1.
• Webster RK, Weinman J, Rubin GJ. Positively Framed Risk Information in Patient Information Leaflets Reduces Side Effect Reporting: A Double-Blind Randomized Controlled Trial. Ann Behav Med. 2018 Oct 22;52(11):920-929. doi: 10.1093/abm/kax064.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 7, 2019
• Primary Completion (ACTUAL): December 20, 2019
• Study Completion (ACTUAL): December 20, 2019

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (ACTUAL): December 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 2, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Acupuncture; Outcome; Placebo; Informed consent; Sham; Delayed Onset Muscle Soreness; Participant information leaflet; Blinding
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Myalgia
• Other Study ID Numbers: KHSIRB-19-173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No