The CRAFT (Chemotherapy Regimen And Fatigue: Touch-Therapy) study was a randomized, three-arm, parallel-comparison pilot clinical trial comparing the effects of a Swedish-style massage regimen to a sham-bodywork control and a usual-care group for fatigue reduction in patients with cancer who were either undergoing chemotherapy or had completed chemotherapy within the previous six months. Participants in the two bodywork arms were assigned to twice-weekly sessions over a six-week period. The primary outcomes assessed were levels of fatigue symptoms and quality-of-life; a qualitative study of outcomes was also included. Outcome assessments occurred at the midpoint and end of the intervention period, one week following the last intervention visit, and six weeks later; overall, participants remained under observation for three months. All procedures were approved by the institutional review boards of the University of California, San Francisco and the Kaiser Foundation Research Institute, Oakland, California.
Participants were adults with a diagnosis of breast, ovarian, colon, or prostate cancer currently undergoing chemotherapy or who had completed chemotherapy within the prior 6 months. We allowed a variety of cancer types to both increase recruitment and to also examine response across different cancers. Since fatigue is a universal symptom across chemotherapy regimens, we felt it appropriate to include all chemotherapies administered for these cancers. Eligible patients had a Karnofsky performance status ≥70 and scored at least 14 on the Modified Schwartz Cancer Fatigue Scale (28
Exclusion criteria included open dermal lesions, history of venous thrombosis, hematocrit <25%, elevated thyroid stimulating hormone, or previous use of oral steroids for more than 3 consecutive months in the prior five years. Patients who had been receiving regular bodywork (at least twice monthly over the prior six months) were also excluded.
The primary outcome measurement was the Revised Piper Fatigue Scale (29
), selected because it had undergone a careful development process (29
), its psychometric properties had been studied and found to be acceptable, it was specifically targeted to the oncology population, was of acceptable length, and addressed the domains that the investigators felt important.
In addition to the Revised Piper Fatigue Scale, the Modified Schwartz Cancer Fatigue Scale (28
) was used as a secondary measure. This scale, also developed specifically for patients with cancer, was a much shorter instrument and was well-suited to telephone screening (hence, its use as an eligibility screening criterion) and for rapid fatigue assessments at each intervention visit.
Additional information collected included a visual analogue scale for overall perceived levels of fatigue, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (a cancer-specific quality-of-life measure) (31
), the Center for Epidemiologic Studies Depression Scale (CES-D) (32
), the Sleep Impairment Index (33
), and a symptomatic side-effect profile. Covariate information collected included regular checks of the participants’ hematocrits to rule out the potential confounding effects of anemia.
Participants were randomized in equal proportions to one of three intervention conditions: an active Swedish-style massage intervention (referred to as the “Medium-Intensity Bodywork” (MIB) arm to the participants), a sham-bodywork intervention (referred to as the “Low-Intensity Bodywork” (LIB) arm), and usual care. Participants in the two bodywork arms were asked to attend two sessions per week (and were strongly encouraged to attend at least once weekly). Prior to each bodywork session, the massage therapist assessed the participant for the presence of a deep venous thrombosis, following a structured exam that included calf circumference measurements (34
We chose a standardized intervention for both treatment arms of the study. These interventions involved a full-body treatment that was completed in approximately 50 minutes; by design, each participant received massages from both male and female massage therapists. Both interventions addressed the same body regions, in the same order, for a specified amount of time. The massage therapists were instructed in both the massage procedure and the sham-touch procedure by the massage therapist co-investigator of the study (MP). Emphasis was placed on consistency in depth of touch and length of time spent on body regions. Because patients receiving massage may report a “hang-over effect” of the positive feelings a massage generates for one-to-two days after the intervention, a twice-weekly protocol (separated by at least one day) seemed most appropriate to maximize a beneficial effect. A six-week duration was chosen because the intervention could be completed before the end of most chemotherapy regimens and we assumed multiple weeks would intensify any positive effects. Moderate and low-intensity procedures were used (as opposed to deeper tissue techniques) because we wished to minimize discomfort and potential bruising of these patients undergoing chemotherapy.
We chose a standardized approach for several reasons. First, a standardized protocol minimized differences among practitioners administering the protocol and ensured that all the participants received as identical an intervention as possible. Importantly, it also limited the comparison between the two intervention groups to one factor (muscle manipulation vs. no muscle manipulation).
The massage protocol was pre-specified and deviations were permitted only for the inability of the participant to tolerate the massage (e.g., participants who were unable to lie supine received massage lying on their side). The intervention was delivered by licensed massage therapists who underwent specific training and who were assessed at regular intervals. Each intervention session was conducted in a private clinical treatment room at the Osher Center for Integrative Medicine Clinic at the University of California, San Francisco.
Because no studies to date had examined whether the effect of massage therapy is specifically from the manipulation of the muscle tissue or from the prolonged touch and contact from a massage therapist, we designed the LIB to control for the environmental conditions and physical contact of the massage arm. The LIB protocol was designed to touch the areas around the major muscle groups without manipulating the muscle tissue directly. Practitioners were instructed to lightly touch an area around a joint or bone region, hold that touch for a period of time, release their hands for a short period of time, adjust to a new position around that same region, and then reapply a light touch. This touch-release-touch method was devised to approximate the amount of time a massage therapist touches a participant during the MIB intervention. By protocol, the practitioners actively touched/massaged the patient during approximately 80% of the intervention time in both bodywork arms of the study.
Participants randomized to the usual-care control arm came to the clinic for their baseline assessment and follow-up interviews but otherwise completed all outcome assessment instruments via mail. Participants in this arm were asked not to receive massage therapy outside of the study during the three-month follow-up period. Participants in the control group were offered compensation for completing their study procedures of either three free massages or monetary compensation at the end of the three-month follow-up period (no compensation was offered to participants in the two bodywork arms).
The detailed protocol descriptions are contained in the Appendix
Recruitment of Therapists
The original intent was to have the massage therapy intervention provided by trained massage therapists and the light-touch control condition performed by oncology nurses. The reasoning for this choice was an attempt to avoid the potential bias that could result from the massage therapists (who could have a vested interest in the outcome of the study) unconsciously doing a better job performing the massage therapy than the control intervention. However, the schedules for the oncology nurses proved too restrictive for this study; the same massage therapists, therefore, performed both the active massage and the control sham-bodywork procedures.
Massage therapists were recruited from local massage-therapy schools and the university-affiliated wellness center. Their training and experience credentials were reviewed by the study investigators and their massage technique was observed prior to appointing them to the study-practitioner positions.
Recruitment of Patients
Recruitment to the trial was carried out at the University of California, San Francisco and the San Francisco facility of the Northern California Kaiser Permanente Health Plan. In addition to passive recruitment, such as posters and fliers, we were also assisted by clinical staff at both institutions who notified potentially eligible patients of the study and the way to access enrollment. The intended sample size for this study was 45 participants.
We also performed a series of in-depth, semi-structured, qualitative interviews at three time points: at the initial randomization visit (during which participants were informed of their randomization assignment), after the final intervention visit (or at six weeks for those participants randomized to the usual-care group), and six weeks after the second interview. Domains assessed in the qualitative interview included physical, social, emotional, and spiritual well-being, definitions and viewpoints regarding participants’ fatigue, and questions regarding their overall study experience.
These interviews were taped, transcribed verbatim, and coded by two researchers (SM and MP). Two of the questions focused on how participants viewed their assigned study intervention. The first question inquired about participants’ feelings regarding their randomization assignment and was asked immediately after participants were told of the study arm to which they were assigned. The second question was asked at the end of the intervention period and assessed the participants’ views regarding the intervention they received during the study. The coded responses were then divided into positive responses, negative responses, or no information available (the question was not asked, the participant didn’t respond, or the participant did not complete that interview).
Experience of Study Participants
One hundred thirteen patients were screened for eligibility and forty-four were randomized over a two-year period. A flowchart of the enrollment of participants is shown in .
Participant flow of CRAFT Study
Participants’ baseline characteristics are shown in . The mean age of the participants was 51 years; the study sample was overwhelmingly female and predominantly white.
Demographic characteristics of CRAFT study participants at randomization.
The study participants’ adherence experience is summarized in . One LIB participant disliked her randomization choice and never appeared for an appointment. Two other LIB-allocated participants withdrew because of the difficulty in keeping twice-weekly appointments. The lone MIB dropout had spotty attendance and did not complete the required number of interview sessions.
Adherence experience in the CRAFT Pilot Study
Three participants (two MIB, one LIB) withdrew for health reasons due to their cancer or chemotherapy regimen. The usual-care control group had the best adherence due to the fact that most of their data collection occurred at home via the mail.
As expected, all of the individuals allocated to the massage intervention had positive responses at the time of randomization; similarly, no negative responses were recorded after the intervention concluded ().
Qualitative analysis of participants’ views of study arm assignment
The LIB group reported mixed reactions to their randomization assignments initially, with some individuals satisfied receiving any intervention, while others were clearly disappointed they did not receive massage (). Thirty-six percent of participants in this arm had a negative viewpoint of being randomized to the LIB group. However, by the end of the intervention, we recorded no negative responses about their participation (although some follow-up data were missing).
The control arm was much more negatively viewed by participants, with 67% showing displeasure at the time of randomization. However this distribution of responses reversed after participation in the study, with 67% of respondents expressing a positive view of the control arm at study closeout. Many participants reported that they enjoyed filling out the questionnaires, stating that it kept them aware of their physical, mental, and emotional states during their chemotherapy treatment.
In summary, the qualitative interviews suggested that, despite some initial negativity regarding the LIB arm, those participants who completed the study viewed both intervention arms positively after the conclusion of the intervention.