To treat patients suffering from CIPN during chemo therapy using accupunture therapy

Phase 3

Completed

• Conditions: Malignant neoplasm of breast of unspecified site,

• Registration Number: CTRI/2021/01/030480
• Lead Sponsor: Tata Memorial Center

Brief Summary

**Methods:**

This was a prospective, single-centre, open-label, phase3, randomized controlled trial done in a tertiary care referral centre, inIndia. The study was plannedwith an open-label design because there were practical challenges inimplementing multiple-level masking, especially, as the acupuncture treatmentis explicitly different than the usual care medications and difficult tointroduce a placebo for acupuncture needles. This study did not involve theadministration of any additional drugs beyond those being used for thepatient’s standard medical care. This study was conducted in accordance with GCP as defined by the International Conference onHarmonization. The study was independently monitored by the data andsafety monitoring board. Data collection and analyses were conducted in asingle institution. Data quality was ensured by regular reviews and audits.Ethics approval was obtained from the Tata Memorial Centre, Mumbai, India.

**Statistical methods and analysis:**

The primary endpoint is to comparethe change in sensory symptom QoL score from baseline to 8 weeks postintervention between the acupuncture and control group. According to Lu et.althe average raw score for sensory scale as assessed using PNQ at baseline forthe usual care arm was 2.5 with a SD of 0.9. For the present study the sensorysymptom score of CIPN20 was considered equivalent to PNQ sensory score. Henceassuming a baseline raw score of 2.5 for sensory scale the correspondingnormalized score (according to EORTC guidelines) was assumed to be 45 atbaseline for the control group of the present study. Lu et al. reported adecrease of 0.3 with a SD of 0.6 points at 8 weeks from baseline in the controlgroup. The corresponding decline in the control group was assumed to be 38.7 at8 weeks. A reduction of 12 points was considered clinically relevant in theacupuncture arm. Simulations were performed by assuming this difference and therespective simulated means in the acupuncture and SoC arm at 8 weeks postintervention was assumed as (27.04+ 23.43) and (38.7 + 23.4). Using ANCOVAprocedure, assuming a power of 80% and significance level of 5%, drop-out rateof 10% and a moderate correlation between baseline and post interventionsensory QoL levels of 0.5, a total of 74 patients (47 patients per group) areneeded.

All raw scores were transformed to a0 to 100 scale according to the algorithms described in the respective scoringmanuals. Continuous data were represented as mean (Standarddeviation) or Median [inter quartile range (IQR)] and categorical data werereported in counts (percentage) respectively. The Shapiro-Wilk’s test was usedto check the normality of each variable. An analysis ofcovariance (**ANCOVA**) model was usedto assess treatment differences in the pain scores after adjusting for ageand baseline scores. The model estimated the mean change in scores and wasreported using 95% CI. Secondary endpoints were analyzed using Linear mixedeffects model to assess the overall change in the scores between the groupsadjusting for age, with time as a within-subject factor and group as abetween-subject factor with respect to domains of QLQ-CIPN20, EORTC QLQ, Totalpain detect scores from baseline to 6 months post-therapy. Logistic regressionanalysis was used to assess the impact of intervention on exploratory outcomeslike incidence of Grade 2 or worse CIPN, presence of musculoskeletal symptoms,hot flashes, and mood swings at 8 weeks, 12 weeks, 18 weeks, and 6 months oftreatment adjusting for the grades at baseline. Odds ratio was reported alongwith 95% CI. All analyses were two-sided, and the level of significance was setat 0.05. All analyses were done in the modified intention-to-treat (mITT)population. Statistical analyses were performed using IBM SPSS Statistics forWindows, Version 25.0. Armonk, NY: IBM Corp and RStudio Version 2023.03.0.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-18
• Study Completion: 2024-04-30
• Last Update Posted: 2024-06-14

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

• 1 Patients with non metastatic breast cancer who have been experiencing grade 1 or greater CIPN for more than 1 week after completion of paclitaxel based chemotherapy 2 Aged 18 or above 3 ECOG performance status 0–1 4 Ability to fill the self-reported questionnaire in any of the three languages (English, Hindi or Marathi).
• 5 Normal blood counts defined as per WHO standards Female: Hemoglobin: 12.0-15.5 grams/dL, TLC-4000-11000 and PLC-1.5 lakhs to4 lakhs.

Exclusion Criteria

• 1 ECOG performance status 2 or above 2 Patients who have hyperalgesia or allodynia 3 Patients having pre-existing causes of peripheral neuropathy like diabetic neuropathy, CKD 4 Patients with bleeding disorders 5 Unstable cardiac disease or myocardial infarction within 6 months prior to study entry 6 Peripheral neuropathy caused by tumor infiltration or compression of spinal nerves or surgical trauma 7 Pregnancy or potential pregnancy and nursing 8 Active clinically significant uncontrolled infection 9 Prior use of acupuncture for CIPN within 6 months prior to study entry 10 Patients with uncontrolled major psychiatric disorders, such as major depression or psychosis, will not be eligible for this trial.
• Patients with a history of depression or anxiety who are stable on or off psychiatric medications will be eligible.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1 Improvement in Quality of life	8 weeks 12 weeks and 6 months from randomisation
To assess the quality of life of the patients at starting of therapy and at 8 weeks of therapy	8 weeks 12 weeks and 6 months from randomisation
2 Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) which has been validated in local languages and would be made available to the patients.	8 weeks 12 weeks and 6 months from randomisation
3 The pain detect questionnaire	8 weeks 12 weeks and 6 months from randomisation
4 EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).	8 weeks 12 weeks and 6 months from randomisation

Secondary Outcome Measures

Name	Time	Method
1 To assess the neuropathy symptoms at 12 weeks and 6 months to see the long lasting effects of acupuncture on peripheral neuropathy	2 To calculate number of patients completing the allocated sittings of acupuncture

Trial Locations

Locations (1)

Tata Memorial Center; 🇮🇳 Mumbai, MAHARASHTRA, India

Tata Memorial Center

🇮🇳Mumbai, MAHARASHTRA, India

Dr Jyoti Bajpai

Principal investigator

02224177287

dr_jyotibajpai@yahoo.co.in