The Effects of Testosterone and Nutritional Supplementation in the Undernourished Elderly

• ClinicalTrials.gov Identifier: NCT00117000
• Recruitment Status: Unknown
• First Posted: July 1, 2005
• Last Update Posted: September 11, 2006
• Sponsor: University of Adelaide
• Collaborator: Organon
• Information provided by: University of Adelaide

Study Description

Brief Summary:

The purpose of this study is to determine what effect treatment for one year with testosterone and a nutritional supplement, alone and combined, has on the adverse effects of under-nutrition in community-dwelling older men and women.

Condition or disease	Intervention/treatment	Phase
Malnutrition; Aging	Drug: testosterone undecanoate	Phase 3

Detailed Description:

We hypothesize that oral androgen therapy and nutritional supplementation will have additive beneficial effects in older malnourished individuals living in the community; there will be a reduction in hospitalizations, falls and weight loss in association with improvements in functional measures and increases in lean body mass. The present study is designed to examine the effect of 12 months oral nutrition supplementation and androgen therapy, alone and combined, on (i) frequency and length of hospitalisations; (ii) functional status; (iii) body composition and weight; (iv) living arrangements; (v) death rate, in community dwelling under-nourished men and women, 65 years and older.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: The Effects of Testosterone and Nutritional Supplementation, Alone and Combined, on the Adverse Effects of Under-Nutrition in the Elderly
• Study Start Date: July 2003
• Study Completion Date: February 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Days in hospital
2. SF-36 quality of life scores (composite physical component score and composite mental component score).

Secondary Outcome Measures :

1. Body composition
2. Muscle strength
3. Number of falls
4. Functional status (living arrangements, activities of daily living and frailty scale scores)
5. Mortality

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women aged 65 years or older who are under-nourished, as defined by a Mini Nutritional Assessment (MNA) score <24 AND 1 or more of the following: *a body mass index (BMI) of less than 22 kg/m2; *weight loss of > 7.5% in the 3 months before enrolling in the study
• Living independently in the community (not in a hospital, nursing home or hostel)
• Understand and sign informed consent document, able to communicate with the investigator, and understand and comply with the requirements of the study.
• Women who are taking oestrogen or other hormone replacement therapy (HRT) may take part (see exclusion criteria for exceptions), as may women who are not taking HRT. If a woman is taking HRT she must have been on a stable dose for at least 3 months before enrolment in the study. If not on HRT, she must not have been taking it for at least 3 months before enrolment.

Exclusion Criteria:

• Dementia as indicated by a Folstein's Mini Mental State Examination (MMSE) score of < 23
• Elevated haematocrit (HCT) levels (>50%)
• Past or present history of prostatic cancer in men (Prostate Specific Antigen (PSA) levels [> age-related normal range and/or irregular prostate on prostate examination]) or breast cancer.
• Pre-existing androgenic signs or symptoms in women of concern to either subject or investigator (deep voice, hirsutism, acne, androgenic hair loss).
• Depression (Yesavage Geriatric Depression Scale (GDS) Score > 11)
• Inability to attend DEXA scan or complete other requirements of the study
• Significant cardiac failure (NYHA Class III and above)
• Significantly abnormal liver function tests (ALT, GGT, bilirubin or ALP more than 2 times the upper limit of normal)
• Nephrotic syndrome; 24h urine protein excretion > 3 grams (if baseline urinalysis reveals > 1+ proteinuria, quantification will be performed) AND/OR calculated creatinine clearance (by the equation of Baracskay and Jarjoura for ambulatory elderly subjects [Cr clearance = 4.4/serum creatinine (mmol/L) + (88-age)](63) < 30 ml/min) AND/OR serum creatinine concentration > 0.2mmol/l.
• Amputee (body mass index, creatinine clearance and body composition estimations inaccurate).
• Any disease, which in the opinion of the investigator is likely to lead to death within one year
• Testosterone or other androgen therapy (including DHEA and tibolone) in the four months before starting the study.
• Medication with cyclosporin or barbiturates

Contacts and Locations

Locations

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Sponsors and Collaborators

University of Adelaide

Organon

Investigators

• Principal Investigator: Ian M Chapman, MBBS, PhD; University of Adelaide

More Information

Publications:

Evans WJ, Campbell WW. Sarcopenia and age-related changes in body composition and functional capacity. J Nutr. 1993 Feb;123(2 Suppl):465-8. doi: 10.1093/jn/123.suppl_2.465. Review.

Tenover JS. Androgen replacement therapy to reverse and/or prevent age-associated sarcopenia in men. Baillieres Clin Endocrinol Metab. 1998 Oct;12(3):419-25. Review.

Roshan S, Nader S, Orlander P. Review: Ageing and hormones. Eur J Clin Invest. 1999 Mar;29(3):210-3. Review.

Volpi E, Sheffield-Moore M, Rasmussen BB, Wolfe RR. Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA. 2001 Sep 12;286(10):1206-12.

Newman AB, Yanez D, Harris T, Duxbury A, Enright PL, Fried LP; Cardiovascular Study Research Group. Weight change in old age and its association with mortality. J Am Geriatr Soc. 2001 Oct;49(10):1309-18.

MacIntosh C, Morley JE, Chapman IM. The anorexia of aging. Nutrition. 2000 Oct;16(10):983-95. Review.

Morley JE. Anorexia in older persons: epidemiology and optimal treatment. Drugs Aging. 1996 Feb;8(2):134-55. Review.

Visvanathan R, Macintosh C, Callary M, Penhall R, Horowitz M, Chapman I. The nutritional status of 250 older Australian recipients of domiciliary care services and its association with outcomes at 12 months. J Am Geriatr Soc. 2003 Jul;51(7):1007-11.

Morley JE. Testosterone replacement and the physiologic aspects of aging in men. Mayo Clin Proc. 2000 Jan;75 Suppl:S83-7. Review.

Melton LJ 3rd, Khosla S, Riggs BL. Epidemiology of sarcopenia. Mayo Clin Proc. 2000 Jan;75 Suppl:S10-2; discussion S12-3. Review.

Roubenoff R, Rall LC, Veldhuis JD, Kehayias JJ, Rosen C, Nicolson M, Lundgren N, Reichlin S. The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin. J Clin Endocrinol Metab. 1998 May;83(5):1502-6.

Davis S. Androgen replacement in women: a commentary. J Clin Endocrinol Metab. 1999 Jun;84(6):1886-91. Review.

Zumoff B, Strain GW, Miller LK, Rosner W. Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab. 1995 Apr;80(4):1429-30.

Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab. 2000 Aug;85(8):2832-8.

Morley JE. Testosterone replacement in older men and women. J Gend Specif Med. 2001;4(2):49-53. Review.

Morley JE. Androgens and aging. Maturitas. 2001 Feb 28;38(1):61-71; discussion 71-3. Review.

Davis SR, Burger HG. The rationale for physiological testosterone replacement in women. Baillieres Clin Endocrinol Metab. 1998 Oct;12(3):391-405. Review.

Tenover JL. Testosterone replacement therapy in older adult men. Int J Androl. 1999 Oct;22(5):300-6. Review.

Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab. 2001 Sep;86(9):4078-88.

Amory JK, Chansky HA, Chansky KL, Camuso MR, Hoey CT, Anawalt BD, Matsumoto AM, Bremner WJ. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. J Am Geriatr Soc. 2002 Oct;50(10):1698-701.

Bakhshi V, Elliott M, Gentili A, Godschalk M, Mulligan T. Testosterone improves rehabilitation outcomes in ill older men. J Am Geriatr Soc. 2000 May;48(5):550-3.

Chakravarti S, Collins WP, Forecast JD, Newton JR, Oram DH, Studd JW. Hormonal profiles after the menopause. Br Med J. 1976 Oct 2;2(6039):784-7.

Zumoff B, Rosenfeld RS, Strain GW, Levin J, Fukushima DK. Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults. J Clin Endocrinol Metab. 1980 Aug;51(2):330-3.

Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas. 1995 Apr;21(3):227-36.

Davis SR, Tran J. Testosterone influences libido and well being in women. Trends Endocrinol Metab. 2001 Jan-Feb;12(1):33-7. Review.

Castelo-Branco C, Vicente JJ, Figueras F, Sanjuan A, Martínez de Osaba MJ, Casals E, Pons F, Balasch J, Vanrell JA. Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women. Maturitas. 2000 Feb 15;34(2):161-8.

Gruber DM, Sator MO, Kirchengast S, Joura EA, Huber JC. Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women. Maturitas. 1998 Jun 17;29(3):253-9.

Padero MC, Bhasin S, Friedman TC. Androgen supplementation in older women: too much hype, not enough data. J Am Geriatr Soc. 2002 Jun;50(6):1131-40. Review.

Lobo RA. Androgens in postmenopausal women: production, possible role, and replacement options. Obstet Gynecol Surv. 2001 Jun;56(6):361-76. Review.

Westaby D, Ogle SJ, Paradinas FJ, Randell JB, Murray-Lyon IM. Liver damage from long-term methyltestosterone. Lancet. 1977 Aug 6;2(8032):262-3.

Raisz LG, Wiita B, Artis A, Bowen A, Schwartz S, Trahiotis M, Shoukri K, Smith J. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab. 1996 Jan;81(1):37-43.

Davis SR, Burger HG. Clinical review 82: Androgens and the postmenopausal woman. J Clin Endocrinol Metab. 1996 Aug;81(8):2759-63. Review.

Burger HG, Hailes J, Menelaus M, Nelson J, Hudson B, Balazs N. The management of persistent menopausal symptoms with oestradiol-testosterone implants: clinical, lipid and hormonal results. Maturitas. 1984 Dec;6(4):351-8.

Burger H, Hailes J, Nelson J, Menelaus M. Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br Med J (Clin Res Ed). 1987 Apr 11;294(6577):936-7.

Miller K, Corcoran C, Armstrong C, Caramelli K, Anderson E, Cotton D, Basgoz N, Hirschhorn L, Tuomala R, Schoenfeld D, Daugherty C, Mazer N, Grinspoon S. Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab. 1998 Aug;83(8):2717-25.

Mortola JF, Yen SS. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab. 1990 Sep;71(3):696-704.

Casson PR, Santoro N, Elkind-Hirsch K, Carson SA, Hornsby PJ, Abraham G, Buster JE. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial. Fertil Steril. 1998 Jul;70(1):107-10.

Phillips E, Bauman C. Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States. Clin Ther. 1997 Sep-Oct;19(5):1070-84.

Barnhart KT, Freeman E, Grisso JA, Rader DJ, Sammel M, Kapoor S, Nestler JE. The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life. J Clin Endocrinol Metab. 1999 Nov;84(11):3896-902.

Diamond P, Cusan L, Gomez JL, Bélanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol. 1996 Sep;150 Suppl:S43-50.

Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000 Sep 7;343(10):682-8.

Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women. J Clin Endocrinol Metab. 2002 Apr;87(4):1509-16.

Myers LS, Dixen J, Morrissette D, Carmichael M, Davidson JM. Effects of estrogen, androgen, and progestin on sexual psychophysiology and behavior in postmenopausal women. J Clin Endocrinol Metab. 1990 Apr;70(4):1124-31.

Watts NB, Notelovitz M, Timmons MC, Addison WA, Wiita B, Downey LJ. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995 Apr;85(4):529-37. Erratum in: Obstet Gynecol 1995 May;85(5 Pt 1):668.

Penotti M, Sironi L, Cannata L, Viganò P, Casini A, Gabrielli L, Vignali M. Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries. Fertil Steril. 2001 Aug;76(2):235-40.

Morley JE. Anorexia of aging: physiologic and pathologic. Am J Clin Nutr. 1997 Oct;66(4):760-73. Review.

Mathey MF, Siebelink E, de Graaf C, Van Staveren WA. Flavor enhancement of food improves dietary intake and nutritional status of elderly nursing home residents. J Gerontol A Biol Sci Med Sci. 2001 Apr;56(4):M200-5.

Rolls BJ, McDermott TM. Effects of age on sensory-specific satiety. Am J Clin Nutr. 1991 Dec;54(6):988-96.

Ritchie CS, Burgio KL, Locher JL, Cornwell A, Thomas D, Hardin M, Redden D. Nutritional status of urban homebound older adults. Am J Clin Nutr. 1997 Oct;66(4):815-8.

Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, Part II: Laboratory evaluation. Nutrition. 2000 Feb;16(2):131-40. Review.

Lumbers M, New SA, Gibson S, Murphy MC. Nutritional status in elderly female hip fracture patients: comparison with an age-matched home living group attending day centres. Br J Nutr. 2001 Jun;85(6):733-40.

Middleton MH, Nazarenko G, Nivison-Smith I, Smerdely P. Prevalence of malnutrition and 12-month incidence of mortality in two Sydney teaching hospitals. Intern Med J. 2001 Nov;31(8):455-61.

Sullivan DH, Walls RC, Lipschitz DA. Protein-energy undernutrition and the risk of mortality within 1 y of hospital discharge in a select population of geriatric rehabilitation patients. Am J Clin Nutr. 1991 Mar;53(3):599-605.

Abbasi AA, Rudman D. Undernutrition in the nursing home: prevalence, consequences, causes and prevention. Nutr Rev. 1994 Apr;52(4):113-22. Review.

de Jong N, Chin A Paw MJ, de Groot LC, de Graaf C, Kok FJ, van Staveren WA. Functional biochemical and nutrient indices in frail elderly people are partly affected by dietary supplements but not by exercise. J Nutr. 1999 Nov;129(11):2028-36.

Lauque S, Arnaud-Battandier F, Mansourian R, Guigoz Y, Paintin M, Nourhashemi F, Vellas B. Protein-energy oral supplementation in malnourished nursing-home residents. A controlled trial. Age Ageing. 2000 Jan;29(1):51-6.

Gray-Donald K, Payette H, Boutier V, Page S. Evaluation of the dietary intake of homebound elderly and the feasibility of dietary supplementation. J Am Coll Nutr. 1994 Jun;13(3):277-84.

Tkatch L, Rapin CH, Rizzoli R, Slosman D, Nydegger V, Vasey H, Bonjour JP. Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. J Am Coll Nutr. 1992 Oct;11(5):519-25.

Delmi M, Rapin CH, Bengoa JM, Delmas PD, Vasey H, Bonjour JP. Dietary supplementation in elderly patients with fractured neck of the femur. Lancet. 1990 Apr 28;335(8696):1013-6.

Schürch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998 May 15;128(10):801-9.

Sullivan DH, Patch GA, Walls RC, Lipschitz DA. Impact of nutrition status on morbidity and mortality in a select population of geriatric rehabilitation patients. Am J Clin Nutr. 1990 May;51(5):749-58.

Baracskay D, Jarjoura D, Cugino A, Blend D, Rutecki GW, Whittier FC. Geriatric renal function: estimating glomerular filtration in an ambulatory elderly population. Clin Nephrol. 1997 Apr;47(4):222-8.

Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, Albarede JL. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition. 1999 Feb;15(2):116-22. Review.

Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98.

Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37-49.

Reuben DB, Siu AL. An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc. 1990 Oct;38(10):1105-12.

Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56.

Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.

Mazess RB, Barden HS, Bisek JP, Hanson J. Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition. Am J Clin Nutr. 1990 Jun;51(6):1106-12.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chapman IM, Visvanathan R, Hammond AJ, Morley JE, Field JB, Tai K, Belobrajdic DP, Chen RY, Horowitz M. Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women. Am J Clin Nutr. 2009 Mar;89(3):880-9. doi: 10.3945/ajcn.2008.26538. Epub 2009 Jan 14.

• ClinicalTrials.gov Identifier: NCT00117000
• Other Study ID Numbers: 030320
• First Posted: July 1, 2005
• Last Update Posted: September 11, 2006
• Last Verified: September 2006

Keywords provided by University of Adelaide:

testosterone; food, formulated; malnutrition; undernutrition; aging; aged; aged, 80 and over; frail elderly

Additional relevant MeSH terms:

Malnutrition; Nutrition Disorders; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents