Melatonin Versus Placebo and the Effect on Appetite in Advanced Cancer Patients

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00513357
• Collaborator: (none)
• Enrollment: 82
• Locations: 2
• Arms: 2
• Duration (Months): 78
• Patients Per Site: 41
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to evaluate the effectiveness of melatonin for the management of poor appetite and weight loss in advanced cancer patients. The effectiveness of melatonin on weight gain, keeping/gaining of lean muscle mass, improved appetite, and side effects will also be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Cancer; Lung Cancer	Drug: Melatonin; Drug: Placebo	Phase 3

Detailed Description

Melatonin is a hormone that is made by the part of the brain called the pineal gland and may help in letting your body know when it is time to go to sleep and when it is time to wake up. The researchers feel melatonin might help to improve your appetite, improve your overall sense of well-being, and maintain your current weight.

If you are found to be eligible to take part in this study, you will see a nutritionist at the first (baseline) visit. The nutritionist will measure the amount of calories you consume. You will be asked to report all food and drinks you have had in a 3-day period. If you are unable to remember what you have eaten and drunk in the last 3 days, you will be asked by the nutritionist to list all the food and drinks you have had within the last 24 hours.

Your arm muscle diameter and your skin fold below your shoulder blade will be measured on the arm you don't normally use to write with. This is to determine your body fat, lean mass and water content of your body.

Your resting energy expenditure will be measured. You will be asked to wear a breathing mask and to blow into a tube. This will allow your breath to be analyzed, to measure how many calories your body is using while you are at rest.

Blood (about 1-2 tablespoons) will be drawn for tests to make sure there are no other treatable causes for your weight loss.

This blood test may not need to be repeated if you have had a blood test in the last 3 months.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of 2 groups. Participants in Group 1 will take melatonin daily before bedtime for 4 weeks. Patients in Group 2 will take a placebo daily before bedtime for 4 weeks. A placebo is a substance that looks like the study drug but which has no active ingredients. You will have an equal chance (50/50) of being placed in either group. Neither you nor any of the medical staff or researchers on this study will know if you are receiving the study drug or placebo.

On Week 2, you will return to the clinic and you will repeat all the tests done at the baseline visit. If you are unable to return to M. D. Anderson to complete the evaluations on Day 14 (± 2 days), the research nurse will contact you by telephone and ask you about any side effects you are experiencing.

At Week 4, you will return to the clinic and all the tests done at baseline will be repeated.

At the end of 4 weeks, all study patients in both groups will be given the opportunity to take melatonin before going to sleep at night for an additional 4 weeks. If you choose not to continue on melatonin for an additional 4 weeks, you will be taken off study and blood will be drawn for your end of study tests which include albumin, C-reactive protein (CRP), thyroid stimulating hormone (TSH), vitamin B-12, and cortisol. These tests will require about 1-2 tablespoons of blood to be drawn. If you choose to continue on melatonin for an additional 4 weeks, you will be asked to return to the outpatient clinic at Week 6 to repeat the tests done at baseline.

Your end of study tests will be done at the end of 8 weeks.

You will continue to visit the study doctor at the outpatient clinic as long he feels it is necessary. At these visits, your height and weight will be recorded and you will be asked what food and drinks you have had.

This is an investigational study. Melatonin is not currently approved by the FDA except to treat blind people with no light perception for sleep disorders-and is considered a food/nutritional supplement. Up to 126 patients will be enrolled at MD Anderson and at Duke University Medical Center in Durham, North Carolina.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Clinical Trial of Melatonin Versus Placebo and the Effect on Appetite in Advanced Cancer Patients
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Melatonin 20 mg of Melatonin before going to sleep at night for a period of 4 weeks.	Drug: Melatonin; 20 mg by mouth daily for 4 Weeks
Placebo Comparator: Placebo 20 mg of Placebo before going to sleep at night for a period of 4 weeks.	Drug: Placebo; Capsule by mouth daily for 4 Weeks

Outcome Measures

Primary Outcome Measures

1. Change in Appetite as Measured by ESAS [Baseline and at 4 weeks]

   Difference in ESAS (Edmonton Symptom Assessment Scale) assessment scores of appetite (symptom) from baseline evaluation [± 3 days] to 4 week evaluation [± 3 days], where the severity at the time of assessment is rated from 0 to 10 on a numerical scale; with 0 meaning that the symptom is absent and 10 that it is the worst possible severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with solid gastrointestinal tumors or lung cancer patients referred to palliative care and a 5% or more involuntary weight loss within the last 6 months with anorexia (>3 on visual analog scale such as ESAS)

2. Greater than or equal to 18 years of age

3. Karnofsky score of 40 or higher

4. Patient has the ability to maintain oral food intake during the study period

5. If patients who have persistent anorexia/cachexia and are currently taking Megace, corticosteroids, non-steroidal anti-inflammatories (NSAID's), or thalidomide, they should be on the medication at least 2 weeks prior to study inclusion

6. Ability to sign informed consent and understand study procedures

7. Patient can continue all medications including complementary therapies or antineoplastic therapy while on-study other than melatonin if they have been on stable dose for at least 2 weeks

8. Negative pregnancy testing in women with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.

9. Patients who cannot take Megace because of past history or elevated risk of DVT, adrenal insufficiency, impotence, hyperglycemia, CHF, menorrhagia, etc.

10. Patients who have persistent anorexia/cachexia after treatment with Megace has failed

Exclusion Criteria:

1. Patients who have dementia or delirium on entry into study as determined by the palliative care specialist using DSM-IV-criteria

2. Patients who are currently taking melatonin

3. Inability to take oral food during the study period

4. Unstable secondary cachexia caused by nausea, diarrhea, taste abnormalities, mucositis, constipation, dysphagia, or clinical depression prior to study inclusion. These symptoms should be resolved or stable for >/= 2 weeks at the time of inclusion into study as determined by the Palliative Care Specialist.

5. Inability to sign informed consent or understand study procedures

6. Karnofsky score of < 40

7. Patients < 18 years of age

8. Patients with </= 5% involuntary weight loss within the last 6 months and anorexia of < 3 on ESAS

9. Patients who are on complementary therapies containing melatonin or on medications for < 2 weeks and not on stable dose

10. Patients who have a cortisol level of </= 4.3 mg/dL at baseline will be excluded, unless they are on replacement corticosteroids.

11. Patients with a TSH of </= 0.50 or >/= 10 mcL/mL at baseline will be excluded

12. Pregnant females or females who are lactating/nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Joan Karnell Cancer Center	Philadelphia	Pennsylvania	United States	19107
2	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Rony Dev, DO, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00513357
• Other Study ID Numbers: 2005-0901
• First Posted: Aug 8, 2007
• Last Update Posted: Dec 11, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Gastrointestinal Cancer; Lung Cancer; Cachexia; Melatonin; Placebo; Anorexia; Weight Loss
• Additional relevant MeSH terms: Gastrointestinal Neoplasms; Melatonin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 07/21/2006 -04/08/2011. All participants recruited at UT MD Anderson Cancer Center.
Pre-assignment Detail	Of the 125 participants, there were 52 participants excluded (43 did not meet inclusion criteria; and 9 declined to participate).

Arm/Group Title	Melatonin	Placebo
Arm/Group Description	20 mg of Melatonin before going to sleep at night for a period of 4 weeks.	20 mg of placebo before going to sleep at night for a period of 4 weeks.
Period Title: Overall Study
STARTED	38	35
COMPLETED	23	25
NOT COMPLETED	15	10

Baseline Characteristics

Arm/Group Title	Melatonin	Placebo	Total
Arm/Group Description	20 mg of Melatonin before going to sleep at night for a period of 4 weeks.	20 mg of placebo before going to sleep at night for a period of 4 weeks.	Total of all reporting groups
Overall Participants	38	35	73
Age (years) [Mean (Full Range) ]
Age range	59	62	59
Sex: Female, Male (Count of Participants)
Female	12 31.6%	15 42.9%	27 37%
Male	26 68.4%	20 57.1%	46 63%
Region of Enrollment (participants) [Number]
United States	38 100%	35 100%	73 100%

Outcome Measures

1. Primary Outcome

Title	Change in Appetite as Measured by ESAS
Description	Difference in ESAS (Edmonton Symptom Assessment Scale) assessment scores of appetite (symptom) from baseline evaluation [± 3 days] to 4 week evaluation [± 3 days], where the severity at the time of assessment is rated from 0 to 10 on a numerical scale; with 0 meaning that the symptom is absent and 10 that it is the worst possible severity.
Time Frame	Baseline and at 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin	Placebo
Arm/Group Description	20 mg of Melatonin before going to sleep at night for a period of 4 weeks.	20 mg of placebo before going to sleep at night for a period of 4 weeks.
Measure Participants	23	25
Mean (Standard Deviation) [units on a scale]	-0.83 (2.6)	-1.19 (2.3)

Adverse Events

Time Frame	4 years and 2 months
Arm/Group Title	Melatonin		Placebo
Arm/Group Description	20 mg of Melatonin before going to sleep at night for a period of 4 weeks.		20 mg of placebo before going to sleep at night for a period of 4 weeks.
All Cause Mortality
	Melatonin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Melatonin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/38 (5.3%)		2/35 (5.7%)
General disorders
Death	2/38 (5.3%)	2	0/35 (0%)	0
Investigations
Alkaline Phosphatase	0/38 (0%)	0	1/35 (2.9%)	1
AST, SGOT	0/38 (0%)	0	1/35 (2.9%)	1
Psychiatric disorders
Confusion	0/38 (0%)	0	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Melatonin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/38 (15.8%)		15/35 (42.9%)
Gastrointestinal disorders
Nausea	1/38 (2.6%)	1	2/34 (5.9%)	2
Constipation	1/38 (2.6%)	1	0/34 (0%)	0
Diarrhea	0/38 (0%)	0	1/34 (2.9%)	1
General disorders
Fatigue	1/38 (2.6%)	1	4/34 (11.8%)	4
Pain	0/38 (0%)	0	3/34 (8.8%)	3
Constitutional Symptom (other)	0/38 (0%)	0	1/34 (2.9%)	1
Pain	1/38 (2.6%)	1	0/34 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/38 (0%)	0	1/34 (2.9%)	1
Nervous system disorders
Somnolence	1/38 (2.6%)	1	1/34 (2.9%)	1
Syncope (Fainting)	0/38 (0%)	0	1/34 (2.9%)	1
Psychiatric disorders
Confusion	1/38 (2.6%)	1	0/34 (0%)	0
Insomnia	0/38 (0%)	0	1/34 (2.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.