The Use of Specialised Amino Acid Mixture in Pressure Ulcer Wound Healing Rates- A Placebo Controlled Trial

Pressure Ulcer Clinical Trial

Official title:

The Use of Specialised Amino Acid Mixture in Pressure Ulcer Wound Healing Rates-A Placebo Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01090076
• Other study ID #: ABOUND
• Status: Completed
• Phase: N/A
• First received: March 18, 2010
• Last updated: June 14, 2013
• Start date: April 2010
• Est. completion date: September 2011

Study information

• Verified date: June 2013
• Source: Changi General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences AuthoritySingapore: Domain Specific Review Boards
• Study type: Interventional

Clinical Trial Summary

This research aims to address the gap in the studies done and test the effects of a commercial mixture of 7 g of Arginine, 7 g Glutamine and 1.2 g HMB* twice a day on hard to heal pressure ulcers in an Asian patient cohort in an acute healthcare setting.

Description:

Pressure ulcers are defined as areas of localised damage to the skin, muscle or underlying tissue, caused by shear, friction or unrelieved pressure, usually over bony prominences. They are associated with many health conditions that cause prolonged bed rest, immobility, inactivity or poor sensation and can significantly contribute to morbidity and mortality, particularly in the aged population. International prevalence rates range widely from 4.6%- 83.6% due to methodological differences and classification systems. In Singapore, a study on the prevalence of pressure ulcers in 3 hospitals revealed a prevalence of 9% to 14%.

Pressure ulcers often fail to heal in a timely and orderly manner, resulting in a chronic non-healing wound. Many intrinsic and extrinsic factors have been identified that can disrupt the wound healing processes of haemostasis, inflammation, proliferation, angiogenesis and remodelling. One of the factors gaining more interest for its impact on wound healing processes is nutritional status.

Arginine is a semi-essential amino acid because even though the body normally makes enough of it, supplementation is sometimes needed during critical illness and severe trauma. There have been numerous research studies focusing on using arginine to enhance wound healing and pressure ulcer prevention. It is required for promotion of nitrogen balance, cell proliferation, T lymphocyte function and collagen accumulation. It also changes into nitric oxide, which is known for its vasodilatory and angiogenic properties.

Glutamine is conditionally essential amino acid because it can be manufactured in the body, but under extreme physical stress the demand for glutamine exceeds the body's ability to make it. Adequate amounts of glutamine are generally obtained through diet alone because the body is also able to make glutamine on its own. Certain medical conditions, including injuries, surgery, infections, and prolonged stress, can deplete glutamine levels. Since glutamine plays a key role in the immune system, a deficiency in this nutrient can significantly slow the healing process.

Beta-hydroxy-Beta methylbutyrate (HMB) is a metabolite of leucine, an essential amino acid. HMB supplementation was associated with increased muscle mass accretion. HMB appears to assert its effect via inhibiting muscle proteolysis and modulating protein turnover.

Recently, arginine has been found to accelerate wound healing in combination with HMB and glutamine. It was shown that healthy subjects who are supplemented orally with arginine had a significant rise in plasma arginine and ornithine levels that led to enhanced rate of collagen synthesis. In another recent study, a HMB/Arginine/Lysine mixture increased protein turnover in elderly patients over a year long period. However, there is no known randomised controlled trial done on patients with chronic hard to heal wounds in acute healthcare settings.

AIM To compare pressure ulcer healing rates in patients supplemented with a commercial HMB/Arginine/Lysine mixture (Abound) and standard high protein, high energy iso-nitrogenous medical nutritional supplements versus patients supplemented with only standard high protein, high energy iso-nitrogenous medical nutritional supplements.

OUTCOME INDICATORS

• Percentage change in wound size (length, depth, area)

• Percentage change in proportion of viable wound tissue (Refer to wound data collection for details)

The study will take on a comparative, randomised controlled trial design.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Patients with pressure ulcers stage II, III or IV, non-healing admitted to Changi General Hospital for > 2 weeks

• Patients who are able to attend outpatient follow-up appointments for dietary and wound review

Exclusion Criteria:

• Age < 21 years old

• Poorly controlled Diabetic Patients (HbA1c >7.0%)

• Patients on Total Parenteral Nutrition

• Patients in MICU/ SICU/ Medically Unstable/ Palliative Care

• Patients with severe Sepsis

• Length of stay < 2 weeks

• Patients who require fluid restriction < 1L/d

• Patients on any other wound healing supplements (e.g. Zinc, Vitamin A and Vitamin C)

• Patients with lower extremity ulcers with untreated peripheral vascular disease

• Patients with deep tissue infection and/or requiring debridement of necrotic or sloughy tissue

• Patients unable to attend outpatient follow-up appointments

• Patients who cannot tolerate oral intake > 70% EER and/or Fluid intake 30ml/kg BW

• Patients who require protein restriction

• Patients who are unable to give consent (absence of next-of-kin)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Pressure Ulcer
• Ulcer

Intervention

Dietary Supplement:
• Abound (7 g of Arginine, 7 g Glutamine and 1.2 g HMB)
Active Arm : Abound x 2 sachets/d (Each sachet provides additional 7g L-Arginine, 7g L-Glutamine, 1.2 g HMB and 79 Kcal) Placebo Arm: Abound(placebo) x 2 sachets/d

Locations

Country	Name	City	State
Singapore	Changi General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Changi General Hospital	Abbott

Country where clinical trial is conducted

Singapore, 

References & Publications (6)

Baier S, Johannsen D, Abumrad N, Rathmacher JA, Nissen S, Flakoll P. Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-lysine. JPEN J Parenter Enteral Nutr. 2009 Jan-Feb;33(1):71-82. doi: 10.1177/0148607108322403. — View Citation

Benati G, Delvecchio S, Cilla D, Pedone V. Impact on pressure ulcer healing of an arginine-enriched nutritional solution in patients with severe cognitive impairment. Arch Gerontol Geriatr Suppl. 2001;7:43-7. — View Citation

Desneves KJ, Todorovic BE, Cassar A, Crowe TC. Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: a randomised controlled trial. Clin Nutr. 2005 Dec;24(6):979-87. Epub 2005 Nov 15. — View Citation

Eley HL, Russell ST, Baxter JH, Mukerji P, Tisdale MJ. Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E923-31. Epub 2007 Jul 3. — View Citation

Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss. Cancer Res. 2005 Jan 1;65(1):277-83. — View Citation

Stechmiller JK, Childress B, Cowan L. Arginine supplementation and wound healing. Nutr Clin Pract. 2005 Feb;20(1):52-61. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	% Viable Tissue	-Percentage viable tissue after 2 weeks; The estimated change in proportion of viable and non-viable tissue was determined using area derived from planimetry via acetate tracings. The description of viable tissue was taken to mean granulating (red) or epithelising (pink) tissue, and non-viable tissue were taken as necrotic (black) or sloughy (green or yellow) tissue.	weeks 1 to 2	No
Primary	% Wound Area Week 1	Percentage change in wound area after week 1	week 0 to 1	No
Primary	% Wound Area Week 2	Percentage change in wound area after week 2	Weeks 1 to 2	No