Adjuvant Melatonin for Prevention of Lung Cancer Recurrence and Mortality (AMPLCaRe)

Adjuvant Melatonin for Prevention of Lung Cancer Recurrence and Mortality: A Randomized Placebo Controlled Clinical Trial

There is evidence to support the use of melatonin, a natural health product, as an additional treatment aid for cancer patients. This study is designed to see if the daily ingestion of 20 milligrams of melatonin for one year can lower the incidence of developing lung cancer recurrence and/or death. Only patients with a diagnosis of non small cell lung cancer who are eligible for surgical resection can participate in the trial. The study will also be assessing for changes in quality of life, pain, fatigue, anxiety, sleep, and depression amongst the participants.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Dietary supplement: melatonin; Dietary supplement: placebo

Detailed Description

The trial employs a two-armed parallel placebo controlled trial design whereby patients with a diagnosis of non small cell lung cancer are randomized to receive either 20 mg of melatonin nightly or an identically matched placebo. All patients will be followed for two years with primary outcomes assessed at a two year time point and secondary outcomes evaluated throughout the course of the trial.

• Study Type: Interventional
• Enrollment (Actual): 709
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut universitaire de Cardiologie et de Pneumologie de Quebec
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 4N7
      • Kelowna General Hospital
    • Surrey, British Columbia, Canada, V3R 7P8
      • Fraser Health
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre/Capital Health
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's/ McMaster University
    • London, Ontario, Canada, N6A 5C1
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 1J7
      • Ottawa General Hospital
    • Toronto, Ontario, Canada, M5G 1Z5
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of non small cell lung cancer
• Eligible for surgical resection
• Willingness to adhere to randomized treatment
• Availability for follow-up schedule of visits

Exclusion Criteria:

• Taking exogenous melatonin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin; To receive 20 mg of melatonin nightly for 1 year post-surgery	Dietary supplement: melatonin; 20 mgs ingested nightly
Placebo Comparator: Placebo; To receive 20 mg placebo nightly for 1 year post-surgery	Dietary supplement: placebo; similar to experimental in all ways except for lack of active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Cancer Recurrence or Mortality - 2 Years	Disease-Free survival (DFS) at 2 years post-surgery. DFS is measured by the number of participants in both arms who have experienced a recurrence OR mortality at 2 years.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	Participant-reported quality of life using the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire C-30 (EORTC QLQ C-30) and Lung Cancer 13 (EORTC QLQ LC13) questionnaires. Scores represent a value from 0-100. Symptom and LC13 scale: 0 represents best health, 100 worst health. Global and functional scales: 100 represents best health, 0 represents worst health. Full scoring algorithms available here: https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf	2 years
Fatigue	Measured using the Multidimensional Fatigue Inventory 20 (MFI-20) questionnaire. Scores are on a scale of 0-100, where 100 is the best health and 0 is the worst health.	2 years
Sleep	Measured using the Medical Outcomes Study (MOS) Sleep Survey. Scales used were Sleep Adequacy and Sleep problems Index II. Scores are on a scale of 0-100. Sleep Adequacy: 100 represents best health; 0 represents worst health. Problems index: 0 represents best health; 100 represents worst health.	2 years
Pain Levels	Calculated using the Brief Pain Inventory. Each scale ranges from 0-10, where 0 is no pain and 10 is the worst possible pain.	3 months
Anxiety	Measured using the Beck Anxiety Inventory. Scored range from 0-63, where 0 is no anxiety and 63 is the worst possible anxiety.	2 years
Depression	Measured using the Beck Depression Inventory II. Scores range from 0-63, where 0 is no depression and 63 is the worst possible depression.	2 years
Adverse Events (Chemotherapy)	Number of participants who experienced an adverse event related to their adjuvant chemotherapy	2 years
Lung Cancer Recurrence or Mortality - 5 Years	Measured as disease-free survival (DFS) at 5 years. DFS was measured by the incidence of a recurrence OR mortality up to 5 years post-surgery.	up to 5 years
Blood Tests to Examine the Effects of Melatonin on the Immune System (Raw Values)	NK cell cytotoxicity changes from baseline to 6 months	6 months
Adverse Events (Radiation)	Number of participants who experienced an adverse event related to their adjuvant radiation therapy	2 years
Blood Tests to Examine the Effects of Melatonin on the Immune System (Comparison Between Groups)	Differences in NK cell cytotoxicity between both arms	6 months

Collaborators and Investigators

• Sponsor: The Canadian College of Naturopathic Medicine
• Collaborators: The Ottawa Hospital; Gateway for Cancer Research; Lotte & John Hecht Memorial Foundation
• Investigators: Principal Investigator: Dugald MR Seely, ND, MSc, The Canadian College of Naturopathic Medicine; Principal Investigator: Andrew JE Seely, MD, The Ottawa Hospital

Publications and helpful links

General Publications

• Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6. doi: 10.1111/j.1600-079X.2005.00258.x.
• Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012 Dec;11(4):293-303. doi: 10.1177/1534735411425484. Epub 2011 Oct 21.
• Seely D, Legacy M, Auer RC, Fazekas A, Delic E, Anstee C, Angka L, Kennedy MA, Tai LH, Zhang T, Maziak DE, Shamji FM, Sundaresan RS, Gilbert S, Villeneuve PJ, Ashrafi AS, Inculet R, Yasufuku K, Waddell TK, Finley C, Shargall Y, Plourde M, Fergusson DA, Ramsay T, Seely AJE. Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial. EClinicalMedicine. 2021 Feb 27;33:100763. doi: 10.1016/j.eclinm.2021.100763. eCollection 2021 Mar.

Helpful Links

• The Canadian College of Naturopathic Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): March 9, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: April 25, 2008
• First Submitted That Met QC Criteria: April 28, 2008
• First Posted (Estimate): April 29, 2008

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: melatonin; lung cancer; randomized clinical trial; natural health product (NHP); complementary and alternative medicine (CAM)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 2007077-01H