L-Arginine Supplements in Treating Women Who Are Cancer Survivors

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00459134
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 186
• Locations: 25
• Arms: 2
• Actual Duration (Months): 37
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: L-arginine supplements may improve the quality of life and sexual function in women who are cancer survivors.

PURPOSE: This randomized clinical trial is studying an L-arginine supplement to see how well it works compared with a placebo in treating women who are cancer survivors.

Condition or Disease	Intervention/Treatment	Phase
Sexual Dysfunction; Sexuality and Reproductive Issues; Unspecified Adult Solid Tumor, Protocol Specific	Dietary Supplement: ArginMax; Dietary Supplement: Placebo	N/A

Detailed Description

OBJECTIVES:

Primary

• Determine whether an L-arginine-based nutritional supplement (ArginMax®) improves the quality of life and sexual function in female cancer survivors.

Secondary

• Compare quality of life of patients treated with ArginMax® vs placebo.

• Compare toxicity of these regimens in these patients.

• Describe the sexual function symptom clusters (if any) in these patients.

OUTLINE: This is a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Patients are stratified according to ECOG performance status (0 or 1 vs 2 or 3), type of malignancy (pelvic vs nonpelvic), and ovarian functional status (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive an oral L-arginine-based nutritional supplement (ArginMax®) twice daily.

• Arm II: Patients receive oral placebo twice daily. In both arms, treatment continues for 12 weeks in the absence of unacceptable toxicity.

Sexual function, quality of life, and toxicity are assessed at baseline and every 4 weeks for 12 weeks.

PROJECTED ACCRUAL: A total of 186 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Study to Determine Whether ArginMax Improves the Sexual Function and Quality of Life in Female Cancer Survivors
• Actual Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: ArginMax ArginMax® 3 pills twice daily	Dietary Supplement: ArginMax; Given orally; Other Names: L-arginine
Placebo Comparator: Arm II: Placebo Patients receive oral placebo 3 pills twice daily	Dietary Supplement: Placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Sexual Function [12 weeks]

   Patients filled out the Female Sexual Function Index (FSFI) at baseline and at 4, 8, and 12 weeks following randomization. The FSFI is comprised of 2 questions related to desire, 4 questions related to arousal, 4 questions related to lubrication, 3 questions related to orgasm, 3 questions related to satisfaction, and 3 questions related to pain. Subscale scores range from 1.2 to 6 (desire) or 0 to 6 (arousal, lubrication, orgasm, and pain) or 0.8 to 6 (satisfaction). A total FSFI score is computed as the sum of the individual subscales; the overall score ranges from 2 to 36. Higher scores indicate better sexual function. The primary outcome comparison is at 12 weeks.

Secondary Outcome Measures

1. Quality of Life [12 weeks]

   Patients filled out the FACT-G quality of life questionnaire at baseline and at 4, 8, and 12 weeks following randomization. The FACT-G questionnaire is comprised of 7 questions related to physical well-being, 7 questions related to social well-being, 6 questions related to emotional well-being, and 7 questions related to functional well-being. Subscale scores range from 0 to 24 (Emotional) or 0 to 28 (Functional, Social, and Physical). A total FACT-G score is computed as the sum of the individual subscales; the overall score ranges from 0 to 108. Higher scores indicate better quality of life. The primary comparison was at 12 weeks.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

Any female cancer survivor who identifies herself as concerned with her sexual quality of life and answering yes to all three of the screening questions.

• Must express interest in sexual activity

• At least 6 months following completion of all cancer therapy. Hormonal therapy and treatment with Herceptin are allowed.

• No evidence of active cancer based on physical exam and/or radiographic images obtained within 3 months of study.

• Absence of any mental, medical or physical disorder know to affect sexual function.

• No participation in another study with an investigational study drug or device during the 30 days prior to start of study drug.

• Lab values must meet the following criteria at study entry: WBC ≥ 2000, Hgb ≥ 10gm/dl, creatinine ≤ 1.5 x ULN, plt ≥ 100,000, T Bili ≤ 1.5

• ECOG performance status must be 0-2.

• Must be able to take oral medication

• Must be 18 years old or older

• Must be minority (non-white) female.

EXCLUSION CRITERIA:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ArginMax.

• Currently taking any blood thinner such as aspirin (one 81mg aspirin, or one baby aspirin per day allowed), Persantine, Heparin, Lovenox, or Coumadin (low dose Coumadin for catheter patency is allowed).

• Patients currently taking Ginkgo Biloba are not allowed on this study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac, arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements and/or ability for sexual function.

• Pregnant women are excluded from this study because ArginMax may be an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ArginMax, breastfeeding should be discontinued if the mother is treated with ArginMax.

• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with ArginMax. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

• Any planned surgery during study participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
2	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
3	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-4000
4	MBCCOP - JHS Hospital of Cook County	Chicago	Illinois	United States	60612
5	CCOP - Central Illinois	Decatur	Illinois	United States	62526
6	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
7	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403-1206
8	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
9	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
10	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
11	CCOP - Beaumont	Royal Oak	Michigan	United States	48073-6769
12	CCOP - Heartland Research Consortium	Saint Louis	Missouri	United States	63131
13	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
14	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65804
15	Hematology Oncology Associates of Central New York, PC - Northeast Center	East Syracuse	New York	United States	13057
16	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
17	Alamance Cancer Center at Alamance Regional Medical Center	Burlington	North Carolina	United States	27216
18	Hugh Chatham Memorial Hospital	Elkin	North Carolina	United States	28621
19	Southeastern Medical Oncology Center - Goldsboro	Goldsboro	North Carolina	United States	27534
20	Caldwell Memorial Hospital	Lenoir	North Carolina	United States	28645
21	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
22	CCOP - Columbus	Columbus	Ohio	United States	43215
23	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
24	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
25	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kathryn M. Greven, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00459134
• Other Study ID Numbers: IRB00001487; U10CA081851; REBACCCWFU 97106
• First Posted: Apr 11, 2007
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: sexual dysfunction; sexuality and reproductive issues; unspecified adult solid tumor, protocol specific

Study Results

Participant Flow

Arm/Group Title	Arm I: ArginMax	Arm II: Placebo
Arm/Group Description	ArginMax® 3 pills twice daily ArginMax: Given orally	Patients receive oral placebo 3 pills twice daily Placebo: Given orally
Period Title: Overall Study
STARTED	94	92
COMPLETED	71	67
NOT COMPLETED	23	25

Baseline Characteristics

Arm/Group Title	Arm I: ArginMax	Arm II: Placebo	Total
Arm/Group Description	ArginMax® 3 pills twice daily ArginMax: Given orally	Patients receive oral placebo 3 pills twice daily Placebo: Given orally	Total of all reporting groups
Overall Participants	94	92	186
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	86 91.5%	83 90.2%	169 90.9%
>=65 years	8 8.5%	9 9.8%	17 9.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51	49	50
Sex: Female, Male (Count of Participants)
Female	94 100%	92 100%	186 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.1%	5 5.4%	6 3.2%
Not Hispanic or Latino	92 97.9%	84 91.3%	176 94.6%
Unknown or Not Reported	1 1.1%	3 3.3%	4 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	20 21.3%	18 19.6%	38 20.4%
White	73 77.7%	73 79.3%	146 78.5%
More than one race	1 1.1%	0 0%	1 0.5%
Unknown or Not Reported	0 0%	1 1.1%	1 0.5%
Region of Enrollment (participants) [Number]
United States	94 100%	92 100%	186 100%

Outcome Measures

1. Primary Outcome

Title	Sexual Function
Description	Patients filled out the Female Sexual Function Index (FSFI) at baseline and at 4, 8, and 12 weeks following randomization. The FSFI is comprised of 2 questions related to desire, 4 questions related to arousal, 4 questions related to lubrication, 3 questions related to orgasm, 3 questions related to satisfaction, and 3 questions related to pain. Subscale scores range from 1.2 to 6 (desire) or 0 to 6 (arousal, lubrication, orgasm, and pain) or 0.8 to 6 (satisfaction). A total FSFI score is computed as the sum of the individual subscales; the overall score ranges from 2 to 36. Higher scores indicate better sexual function. The primary outcome comparison is at 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who filled out the FSFI at any time

Arm/Group Title	Arm I: ArginMax	Arm II: Placebo
Arm/Group Description	ArginMax® 3 pills twice daily ArginMax: Given orally	Patients receive oral placebo 3 pills twice daily Placebo: Given orally
Measure Participants	93	90
Least Squares Mean (Standard Error) [units on a scale]	17.81 (0.90)	17.15 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: ArginMax, Arm II: Placebo
	Comments	The null hypothesis is that sexual function will be the same in both groups at 12 weeks. A Mixed effect repeated measures model constrained such that the baseline means were equal in the two groups was used to test this hypothesis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.576
	Comments	This p-value is not adjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments	Mixed effect repeated measures model constrained such that the baseline means were equal in the two groups.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; -1.67 to 3.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.19
	Estimation Comments

2. Secondary Outcome

Title	Quality of Life
Description	Patients filled out the FACT-G quality of life questionnaire at baseline and at 4, 8, and 12 weeks following randomization. The FACT-G questionnaire is comprised of 7 questions related to physical well-being, 7 questions related to social well-being, 6 questions related to emotional well-being, and 7 questions related to functional well-being. Subscale scores range from 0 to 24 (Emotional) or 0 to 28 (Functional, Social, and Physical). A total FACT-G score is computed as the sum of the individual subscales; the overall score ranges from 0 to 108. Higher scores indicate better quality of life. The primary comparison was at 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who filled out the FACT-G at any time

Arm/Group Title	Arm I: ArginMax	Arm II: Placebo
Arm/Group Description	ArginMax® 3 pills twice daily ArginMax: Given orally	Patients receive oral placebo 3 pills twice daily Placebo: Given orally
Measure Participants	93	92
Least Squares Mean (Standard Error) [units on a scale]	89.96 (1.38)	85.47 (1.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: ArginMax, Arm II: Placebo
	Comments	The null hypothesis was that quality of life would be the same in both groups at 12 weeks. A mixed effect repeated measures model constrained such that the baseline means were equal in the two groups was used to test this hypothesis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	This p-value is not adjusted for multiple comparisons.
	Method	Mixed Models Analysis
	Comments	Mixed effect repeated measures model constrained such that the baseline means were equal in the two groups.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.49
	Confidence Interval	(2-Sided) 95%; 1.09 to 7.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.73
	Estimation Comments

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	The sample size for this section is the number of participants who had post-randomization toxicity data.
Arm/Group Title	Arm I: ArginMax		Arm II: Placebo
Arm/Group Description	ArginMax® 3 pills twice daily ArginMax: Given orally		Patients receive oral placebo 3 pills twice daily Placebo: Given orally
All Cause Mortality
	Arm I: ArginMax		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I: ArginMax		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/79 (7.6%)		4/77 (5.2%)
Gastrointestinal disorders
Pain - Abdomen	1/79 (1.3%)	1	0/77 (0%)	0
General disorders
Hot Flashes	3/79 (3.8%)	6	3/77 (3.9%)	4
Infections and infestations
Infection - Vulva	1/79 (1.3%)	1	0/77 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/79 (0%)	0	1/77 (1.3%)	1
Nervous system disorders
Headache	1/79 (1.3%)	1	0/77 (0%)	0
Psychiatric disorders
Insomnia	1/79 (1.3%)	1	0/77 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I: ArginMax		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/79 (81%)		60/77 (77.9%)
Gastrointestinal disorders
Nausea	5/79 (6.3%)	6	8/77 (10.4%)	11
General disorders
Headache	20/79 (25.3%)	28	25/77 (32.5%)	46
Hot Flashes	56/79 (70.9%)	128	43/77 (55.8%)	107
Nervous system disorders
Neuropathy	19/79 (24.1%)	38	11/77 (14.3%)	27

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.