Effect of Testosterone on Elderly Frail Men With Testosterone Deficiency

Effect of Testosterone on Elderly Frail Men With Testosterone Deficiency - a Double-blinded, Randomized and Placebo-controlled Intervention Study

The purpose of this study is to increase the functional level of the elderly to thereby reduce fall risk, improve motor skills, and increase psychological well-being, as well as to assess whether the restoration of a normal testosterone level contributes to a faster recovery. The effect of testosterone is investigated as measured by physical and mental functional capacity, including cognition, in hypogonadal elderly men with a significant loss of function. The study is aimed at participants who are too weak to participate in the progressive strength training.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypogonadal Males; Falls (Accidents) in Old Age; Frail Elderly Patients; Testosterone Replacement Therapy
• Intervention / Treatment: Drug: Nebido (Testosterone Undecanoate)

Detailed Description

Please see the uploaded study protocol.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rune S. Rasmussen, MSc, PhD; Phone Number: +4528757500; Email: rsr@sund.ku.dk
• Study Contact Backup: Name: Karsten Overgaard, MD, Neurologist; Phone Number: 26172611; Email: Karsten.Overgaard@regionh.dk

Study Locations

• Denmark
  • Holbæk, Denmark, 4300
    • Holbæk Hospital
    • Contact: Mette Midttun, MD, DMSc; Phone Number: 45 - 20186174; Email: memid@regionsjaelland.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men aged 70 or over.
• Living at home in their own home or in sheltered housing.
• Independent walking function, possibly with a walking aid.
• Able to perform the chair-stand test a maximum of 8 times in 30 seconds or Timed Up and Go (TUG) of at least 30 seconds.
• There must be at least 3 symptoms of frailty or objective findings.
• Serum testosterone < 10 nmol/L as an average of 2 independent measurements at the Center for Growth and Reproduction, Rigshospitalet.

Exclusion Criteria:

• Known or previous prostate cancer.
• Abnormally elevated serum PSA (PSA = prostate-specific antigen) corresponding to PSA > 5 ng/ml or PSA > 0.15 ng/ml/cc (relative to prostate size in cubic centimeters (cc)).
• Hemochromatosis.
• Heart diseases in the form of: Peri-, myo-, or endocarditis, angina pectoris, severe heart failure (NYHA class III and IV), severe hypertension (systolic BP > 180 or diastolic BP > 105 mmHg after possible antihypertensive treatment). - Resting dyspnea.
• Liver (ASAT > 2 x upper normal limit) or renal insufficiency (serum creatinine > 200 micromol/l).
• Severe intractable epilepsy or migraine.
• Insulin treatment.
• Previous or current bisphosphonate, fluoride, HRT, SERM, strontium, teriparatide, or more than 3 weeks of prednisolone treatment.
• Joint disease with acute inflammation.
• Active cancer disease, in chemo- or radiotherapy.
• Bone metabolic disease except for age-related osteoporosis.
• Autoimmune diseases, chronic systemic diseases (cirrhosis, AIDS, chronic renal failure).
• Primary testosterone deficiency in the form of testicular dysgenesis, Klinefelter syndrome (47,XXY), 46,XX males, LH resistance, Y chromosome deletions, other sex chromosome abnormalities.
• Significant abuse, mental illness, dementia, physical handicaps with inability to complete the intervention or tests, or to give informed consent.
• Contraindications for testosterone undecanoate are thus included in exclusion criteria, such as the presence of liver tumors, breast carcinoma, and prostate cancer, for which trial participants will be examined before the start of the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Placebo; Patients receiving placebo
Active Comparator: Intervention; Patients receiving testosterone undecanoate	Drug: Nebido (Testosterone Undecanoate); Testosterone supplementation is given intramuscularly with 1000 mg testosterone undecanoate, which has an effect for approx. 12 weeks, but which can be repeated more frequently between the 1st and 2nd administration. The injection is thus repeated in week 6. 3 injections per trial subject are expected, i.e., in weeks 1, 6, and 16. If the participants are motivated to continue so that long-term effects can be measured, the participants will be asked in week 12 whether they wish to continue to week 52. Upon acceptance of continuation to week 52, testosterone and placebo injections are offered according to original groups in weeks 26, 36, and 46, after which testing of primary and secondary endpoints is not only performed in week 20 but also in week 52.; Other Names: Intervention; Experimental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chair-stand test	A measure of general strength in extremities. Number of times the participant can stand up and sit down from a chair in 30 seconds. A good correlation (r=0.78) has been found with leg press and acceptable test-retest reliability (ICC=0.86). It has recently been scientifically documented that the ability among elderly persons to perform this simple test correlates with the risk of serious fall accidents	At weeks 0, 4 and 20.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of fall frequency and severity	Registered via a questionnaire for each trial subject and is also included in the monitoring of adverse events.	At weeks 0, 4 and 20.
Balance ability	Tested via the Tandem test, which contains three starting positions: 1) Standing with feet together, standing in semi-tandem stance, and standing in tandem stance.	At weeks 0, 4 and 20.
Avlund's mobility scale	Questions about experiencing fatigue and need for support in common activities of daily living. Avlund's mobility scale is correlated with isometric muscle strength, simple functional tests, increased risk of hospitalizations, and mortality. Good inter- and intra-reliability (kappa 0.72-1.00) has been shown. Scores range from 0 to 6, and higher scores indicate worse outcome.	At weeks 0, 4 and 20.
Geriatric Depression Scale (GDS)	Questionnaire about depression and psychological well-being. Scores range from 0 til 15. Score below 5 are normal, while scores of 5 or higher indicate varying degrees of depression, scoring 13-15 indicates severe depression.	At weeks 0, 4 and 20.
Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment is a cognitive screening instrument which provides an estimate of the level of intellectual functioning. Scores are from 0 to 30, where a score of 26 or higher is considered normal. Montreal Cognitive Assessment is moreover sensitive to mild cognitive problems as well as dementia. Studies have shown that Montreal Cognitive Assessment is more sensitive than Mini Mental State Examination to detecting mild cognitive changes and is as effective in identifying the incidence of Alzheimer's disease.	At weeks 0, 4 and 20.
Mini Mental State Examination (MMSE)	Cognitive screening test that provides an estimate of the intellectual functional level. This test is included as it is performed as standard at the Geriatric Outpatient Clinic. Combined, MMSE and MoCA provide a broader assessment of cognitive functional level. Scores range from 0 to 30, higher scores indicate better cognitive status. Scores from 26 to 30 are considered normal.	At weeks 0, 4 and 20.
Quality of life EQ-5D	Questionnaire about perceived quality of life. Scores range from 0 to 1 (first scale) and from 0 to 100 (second scale). Higher scores indicate better quality of life.	At weeks 0, 4 and 20.
Clinical Frailty Scale (CFS)	General assessment of health and functional level in the elderly. Scoring ranges from 1 to 9, and higher scores indicate more frailty.	At weeks 0, 4 and 20.
Falls Efficacy Scale - International (FES-I, Fear of falling). Scores range from 16 to 64, and higher scores indicate increased anxiety of having a severe fall accident.	Assessment of fall risk in the elderly.	At weeks 0, 4 and 20.

Collaborators and Investigators

• Sponsor: Rune Skovgaard Rasmussen
• Investigators: Principal Investigator: Mette Midttun, MD, DMSc, Holbaek Sygehus

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: frailty; hypogonadism; falls; testosterone replacement therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Gonadal Disorders; Pathological Conditions, Signs and Symptoms; Frailty; Hypogonadism; Investigative Techniques; Methods; testosterone undecanoate
• Other Study ID Numbers: H-16020521

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: If there is interest, we will consider sharing data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No