Efficacy of Caffeine Injection as an Adjuvant to Opioid Therapy in Cancer Pain

Efficacy of Caffeine as an Adjuvant to Opioid Therapy in Cancer Pain: a Randomized, Double-blind, Placebo-controlled Trial

Pain is a most common symptom and it has a high impact on quality of life in cancer patients. Many cancer patients have received opioid therapy, but also many of them have suffered from side effects of opioids. Drowsiness and confusion are common side effects of opioids. Caffeine is a well known psychostimulant,and it is widely used as an analgesics. Thus, the investigators aimed to prove the efficacy of intravenous caffeine administration as an adjuvant analgesics to opioids. At the same time, the investigators tried to find that the side effects of opioids could be ameliorated by caffeine.

Study Overview

• Status: Completed
• Conditions: Pain; Cancer
• Intervention / Treatment: Drug: Caffeine; Drug: Normal saline

Detailed Description

Previous studies on cancer pain lacked assessment of quality of life. And most of previous studies on cancer pain did not give attention to symptoms accompanied with pain. We include such variables as outcome measures, and aimed to evaluate the efficacy and the safety of intravenous caffeine in advanced cancer inpatients.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of
      • National Health Insurance Corporation Ilsan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced (Stage IV) cancer inpatients
• Adults aged over 18 years
• Patients who have received opioid therapy and whose pain scales are under 6 (by numeric rating scale)
• Patients who do not take caffeine beverage 48 hours before study period
• Volunteers who provided written informed consent

Exclusion Criteria:

• Sensitivity (palpitation,headache,irritability,insomnia) to caffeine
• Uncontrolled hypertension and/or heart disease
• Liver failure (alanine aminotransferase >= 100 IU/L)
• Kidney failure (serum creatinine >= 2.0 mg/dL)
• Patients taken theophylline
• Gastroesophageal reflux disease
• Chronic glaucoma
• Cognitive impairment
• Progressive pain over 7 (by numeric rating scale)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caffeine; Intravenous injections of 200mg of caffeine with 100ml of normal saline over 1 hour	Drug: Caffeine; Intravenous injection of caffeine 200mg with 100ml of normal saline over 1 hour, once a day, for two days.; Other Names: Caffeine sodium benzoate
Placebo Comparator: Placebo; Intravenous injections of 100ml of normal saline over 1 hour	Drug: Normal saline; Intravenous injections of 100ml of normal saline over 1 hour, once a day, for two days; Other Names: 0.9% saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating of Scale (From 0 to 10) of Pain and Possible Side Effects (Drowsiness, Confusion, Nausea) of Opioids	Scores were measured by Numeric Rating Scale. Scores range from 0 to 10; higher scores represent higher levels of pain, and possible side effects (drowsiness, confusion, nausea) of opioids.	two days
Numeric Rating of Scale (From 0 to 10) of Possible Sleep Disturbance of Opioids	Scores were measured by Numeric Rating Scale. Scores range from 0 to 10; a higher score represents a higher level of sleep disturbance.	two days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of Fatigue at the Point of Time With Numeric Rating Scale From 0 to 10	Scores were measured by Numeric Rating Scale. Scores range from 0 to 10; a higher score represents a higher level of fatigue.	two days
Health-related Quality of Life	Scores were measured by Numeric Rating Scale. Scores range from 0 to 10; a higher score represents a better health-related quality of life.	two days
Impact of Symptom Burden to Daily Life (by MD Anderson Symptom Inventory-Korean)	Scores were measured by Numeric Rating Scale. Scores range from 0 to 10; a higher score represents a higher level of impact of symptom burden to daily life.	two days

Collaborators and Investigators

• Sponsor: Korea Research Foundation
• Collaborators: Korea University Guro Hospital
• Investigators: Principal Investigator: Sang-Yeon Suh, M.D.,Ph.D, DongGuk University

Publications and helpful links

General Publications

• Mercadante S, Serretta R, Casuccio A. Effects of caffeine as an adjuvant to morphine in advanced cancer patients. A randomized, double-blind, placebo-controlled, crossover study. J Pain Symptom Manage. 2001 May;21(5):369-72. doi: 10.1016/s0885-3924(01)00249-4.
• Manfredi PL, Gonzales GR. Symptomatic uses of caffeine in patients with cancer. J Palliat Care. 2003 Spring;19(1):63-5. No abstract available.
• Bruera E, Watanabe S. Psychostimulants as adjuvant analgesics. J Pain Symptom Manage. 1994 Aug;9(6):412-5. doi: 10.1016/0885-3924(94)90179-1.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: April 9, 2009
• First Submitted That Met QC Criteria: April 9, 2009
• First Posted (Estimate): April 10, 2009

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 3, 2011
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Pain; Quality of life; Fatigue; Sedation; Confusion; Caffeine; Cancer patients; Adjuvant analgesics
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Antifungal Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine; Sodium Benzoate
• Other Study ID Numbers: E00058; GR0857-006 (Other Identifier: Korea University Guro Hospital); SuYeon2009-08 (Other Identifier: National Health Insurance Corporation Ilsan Hospital)