NCT04505553

Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer

Completed Phase 2 Results posted Last updated 21 January 2026

What this trial tests

Phase 2 trial testing Acupuncture Therapy in Appendix Carcinoma in 78 participants. Completed in 31 March 2024.

Timeline

1 June 2021

Primary endpoint
7 March 2024

31 March 2024

Quick facts

Lead sponsor	University of Washington
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	supportive care
Enrollment	78
Start date	1 June 2021
Primary completion	7 March 2024
Estimated completion	31 March 2024
Sites	1 location across United States

Drugs / interventions tested

• Acupuncture Therapy
• Acupressure Therapy
• Oral Cryotherapy
• Questionnaire Administration
• Quality-of-Life Assessment

Conditions studied

• Appendix Carcinoma — all drugs for Appendix Carcinoma →
• Colon Carcinoma — all drugs for Colon Carcinoma →
• Esophageal Carcinoma — all drugs for Esophageal Carcinoma →
• Gastric Carcinoma — all drugs for Gastric Carcinoma →

Sponsor

University of Washington

Who can join

18 and older, any sex, with Appendix Carcinoma or Colon Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Severity of Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline to 3 Months Primary · At 3 months

Measured by the European Organization for Research and Treatment of Cancer (EORTC)-CIPN 20. Severity of CIPN will be summarized for each treatment arm, and treatment comparisons made via linear regression model with adjustment for baseline severity level. The EORTC QLQ-CIPN20 is a 20-item questionnaire that evaluates CIPN using 3 subscales that assess sensory (9 items), motor (8 items), and autonomic (3 items) symptoms and functioning. The CIPN-20 subscale raw scores are linearly converted to a 0-100 scale such that a high score corresponds to a worse condition or more symptoms. Change in seve

Sensory Subscale

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	5.9	-7.4 – 37.0
Arm II (Cryotherapy)	9.1	-11.1 – 25.9

Motor Subscale

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	1.9	-16.7 – 12.5
Arm II (Cryotherapy)	5.7	-4.2 – 25.0

Autonomic Subscale

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	0.6	-33.3 – 22.2
Arm II (Cryotherapy)	0.8	-50.0 – 44.4

Number of Participants With Grade 2 or Higher Chemotherapy-Induced Peripheral Neuropathy Secondary · 3 months

Measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5. Incidences of CIPN (grade 2 or higher), pain, fatigue, nausea, and anxiety will be compared between treatment arms using Chi-squared or Fisher's exact tests as appropriate.

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	28
Arm II (Cryotherapy)	33
Arm I (Acupuncture, Acupressure, Cryotherapy)	5
Arm II (Cryotherapy)	3

Severity of CIPN: Neuropen Assessment of Patients' Perceived Pressure Secondary · 3 months

The Neuropen is used to assess pressure perception. Pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot at each of the ten different sites recorded as present or absent. The proportion present was calculated for each patient at baseline and at 3 months. The difference between these proportions from baseline to 3 months was calculated for each patient. The mean of these differences was calculated within each arm and the difference of those means was then compared between arms.

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-1.0	± 4.4
Arm II (Cryotherapy)	-0.7	± 7.3

Severity of CIPN: Tuning Fork Vibration Sensation Testing Secondary · 3 months

A study-specific 128-Hz tuning fork will be used to assess vibration sensation on the great toe at baseline and 3 months. The time in seconds to loss of vibration sensation was measured. Vibration sensation is lost sooner in CIPN, which means that shorter duration of vibration scores are associated with increased CIPN. The difference from baseline to 3 months in number of seconds to loss of vibration sensation was calculated for each patient. The differences were averaged across patients in each arm. The mean differences were compared between arms.

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-5.0	± 11.6
Arm II (Cryotherapy)	0.1	± 6.6

Proportion of Patients Assigned to the Intervention Arm Who Complete 60% of Acupuncture Treatments Secondary · 3 months

Adherence to acupuncture treatment among patients in the intervention arm will be described as a proportion with 95% confidence interval. Reasons for treatment non-adherence and delivered dose intensity of chemotherapy will be noted.

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	23
Arm I (Acupuncture, Acupressure, Cryotherapy)	10

Change in Severity of Pain, Fatigue, Nausea, and Anxiety From Baseline to 3 Months Secondary · 3 months

Measured by patient-reported National Cancer Institute \[NCI\] Patient Reported Outcomes \[PRO\]-CTCAE. The change in severity from baseline to 3 months was calculated and it ranged from -3 to 3. The severity was measured on a 0-3 (0=None, 3=Severe) scale with a higher value representing a worse outcome and a lower value representing a better outcome. This was done separately for pain, fatigue, nausea, and anxiety.

Pain

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-0.3	± 1.2
Arm II (Cryotherapy)	-0.3	± 1.1

Fatigue

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-0.1	± 0.9
Arm II (Cryotherapy)	0.4	± 1.2

Nausea

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-0.3	± 0.7
Arm II (Cryotherapy)	0.3	± 1.0

Anxiety

Group	Value	95% CI
Arm I (Acupuncture, Acupressure, Cryotherapy)	-0.1	± 1.0
Arm II (Cryotherapy)	-0.1	± 0.9

Adverse events — posted to ClinicalTrials.gov

Time frame: 22 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Acupuncture, Acupressure, Cryotherapy)

Serious: 0/33 (0%)

Deaths: 5/33

Arm II (Cryotherapy)

Serious: 0/36 (0%)

Deaths: 3/36

Other adverse events (45 terms — click to expand)

Reaction	System	Arm I (Acupuncture, Acupre…	Arm II (Cryotherapy)
Fatigue	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Peripheral Sensory Neuropathy	Nervous system disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Paresthesia	Nervous system disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Oral Symptoms	Gastrointestinal disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Other Body Pain	Musculoskeletal and connective tissue disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Dysarthria	Nervous system disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Edema Limbs	General disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
White Blood Cell Decreased	Investigations	—	—
Headache	Nervous system disorders	—	—
Eye Pain	Eye disorders	—	—
Gastroesophageal Reflux Disease	Gastrointestinal disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Peripheral Motor Neuropathy	Nervous system disorders	—	—
Rash Acneiform	Skin and subcutaneous tissue disorders	—	—
Rectal Hemorrhage	Gastrointestinal disorders	—	—
Upper Respiratory Infection	Infections and infestations	—	—
Anxiety	Psychiatric disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Blurred Vision	Eye disorders	—	—
Hiccups	Respiratory, thoracic and mediastinal disorders	—	—
Hot Flashes	Vascular disorders	—	—
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	—	—
Small Intestinal Obstruction	Gastrointestinal disorders	—	—
Other Surgical and Medical Procedures	Surgical and medical procedures	—	—
Confusion	Psychiatric disorders	—	—
Aspartate Aminotransferase Increased	Investigations	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Dysuria	Renal and urinary disorders	—	—
Hoarseness	Respiratory, thoracic and mediastinal disorders	—	—

Data from ClinicalTrials.gov NCT04505553 adverse events section.

Sponsor's own description

This phase II trial investigates how well oral cryotherapy plus acupressure and acupuncture compared with oral cryotherapy alone work in decreasing chemotherapy-induced peripheral neuropathy in patients with gastrointestinal cancer who are receiving oxaliplatin-based chemotherapy. Acupressure is the application of pressure or localized massage to specific sites on the body to control symptoms such as pain or nausea. Acupuncture is the technique of inserting thin needles through the skin at specific points on the body to control pain and other symptoms. Cryotherapy uses cold temperature such as oral ice chips to prevent abnormally increased pain sensation. Giving oral cryotherapy with acupressure and acupuncture may work better in decreasing chemotherapy-induced peripheral neuropathy from oxaliplatin-based chemotherapy in patients with gastrointestinal cancer compared to oral cryotherapy alone.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.
   Tsai CH, Lin YH, Li YS, Ho TL, et al · · 2021 · cited 12× · PMID 34502166 · DOI 10.3390/ijms22179257
2. Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibilit
   Cohen SA, Veleber S, Siman J, Guthrie KA, et al · · 2023 · cited 5× · PMID 37380021 · DOI 10.1016/j.cct.2023.107273