AIM-TEST: Microbiome-Targeted Nutrition for Functional Secondary Hypogonadism

NCT07761546 | Enrolling By Invitation

• 1 other identifier: Enbiosis_AIM-TEST
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

AIM-TEST is a randomized, double-blind, placebo-controlled clinical trial evaluating whether an AI-guided, microbiome-targeted nutritional intervention can increase the body's own testosterone production in men aged 30-65 years with symptomatic, biochemically confirmed functional secondary hypogonadism. Functional secondary hypogonadism is characterized by symptoms of testosterone deficiency together with repeatedly low morning testosterone levels and low or inappropriately normal gonadotropin levels, without evidence of primary testicular failure or an organic hypothalamic or pituitary disorder. Men may be included regardless of their body weight or obesity status, provided that their low testosterone has been appropriately confirmed and does not require urgent disease-specific or hormonal treatment. Participants will be randomly assigned to receive either the active nutritional supplement or a matched placebo once daily for 12 weeks. The main question is whether the active intervention produces a greater increase in morning total testosterone than placebo. The study will also assess calculated free testosterone, symptoms of androgen deficiency, sexual function, metabolic and inflammatory markers, gut microbiome changes, treatment tolerability, and safety. Participants will be followed for an additional 12 weeks after stopping the study product to explore whether any observed effects are maintained. The study hypothesis is that the microbiome-targeted intervention will result in a greater improvement in endogenous testosterone levels than placebo. This is a proof-of-concept study and is not intended to replace standard diagnostic evaluation or established treatment when these are clinically required.

Conditions

Hypogonadism, Male; Secondary Hypogonadism

Keywords

Hypogonadism; Microbiome; Gut microbiome; Testosterone; Male sexual health; Erectile dysfunction; Functional secondary hypogonadism; Male hypogonadism; Testosterone deficiency; Nutritional supplement; Microbiome-targeted nutritional intervention; Artificial intelligence

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Mean Fasting Morning Serum Total Testosterone at Week 12

  Serum total testosterone will be measured in nmol/L at a central laboratory. The baseline value will be the arithmetic mean of two fasting morning samples collected on separate days 2-7 days apart before randomization. The Week 12 value will be the arithmetic mean of two fasting morning samples collected 2-7 days apart during the end-of-intervention assessment. Both Week 12 samples will be collected before the daily dose and before discontinuation of the assigned study product. The outcome will be calculated as the Week 12 mean minus the baseline mean. Positive values indicate an increase in total testosterone.

  Baseline to the end of the 12-week

Secondary Outcomes (7)

• Mean Change From Baseline in Male Andropause Symptoms Self-Assessment Questionnaire Total Score at Week 12

  Baseline to Week 12

• Mean Change From Baseline in Calculated Free Testosterone at Week 12

  Baseline to Week 12

• Number of Participants With at Least a 20 Percent Increase in Mean Total Testosterone at Week 12

  Baseline to week 12

• Number of Participants With Mean Fasting Morning Serum Total Testosterone of at Least 12.0 nmol/L at Week 12

  Baseline to week 12

• Number of Participants With Patient Global Impression of Improvement Response at Week 12

  Baseline to week 12

Other Outcomes (10)

• Mean Change From Baseline in Fasting Morning Serum Total Testosterone at Week 24

  Baseline to Week 24, following approximately 12 weeks without study product

• Mean Change From Baseline in Male Andropause Symptoms Self-Assessment Questionnaire Total Score at Week 24

  Baseline to Week 24, following approximately 12 weeks without study product

• Mean Change From Baseline in Calculated Free Testosterone at Week 24

  Baseline to Week 24, following approximately 12 weeks without study product

Study Arms (2)

Microbiome-targeted oral food supplement

EXPERIMENTAL

Participants assigned to this arm will receive a fixed-formula, microbiome-targeted oral nutritional supplement consisting of one sachet and one capsule administered once daily for 12 weeks. All participants will receive the same standardized formulation; the intervention will not be personalized or modified according to individual microbiome findings. The 12-week intervention period will be followed by a 12-week intervention-free follow-up period.

Dietary Supplement: Fixed-Formula Microbiome-Targeted Oral Nutritional Supplement

Matching placebo oral supplement

PLACEBO COMPARATOR

Participants assigned to this arm will receive a matched placebo consisting of one sachet and one capsule administered once daily for 12 weeks, followed by a 12-week intervention-free follow-up period. The placebo will be matched as closely as feasible to the active intervention in packaging, appearance, weight, taste, odor, mouthfeel, and administration schedule. It will be designed not to contain nutritional components expected to meaningfully affect testosterone regulation, the gut microbiome, or the principal metabolic and hormonal outcomes evaluated in the study. The final placebo composition will be defined in the approved product specification.

Dietary Supplement: Matched Oral Placebo

Interventions

Fixed-Formula Microbiome-Targeted Oral Nutritional Supplement DIETARY_SUPPLEMENT

A fixed-formula, microbiome-targeted oral nutritional supplement administered as one sachet and one capsule once daily for 12 weeks. The formulation was developed through an AI-guided evaluation of microbiome-related biological pathways and candidate nutritional components. All participants assigned to the experimental arm will receive the same standardized formulation; the intervention will not be personalized or modified according to individual microbiome findings during the study. The 12-week intervention period will be followed by a 12-week period without study product. The complete qualitative and quantitative formulation, ingredient standardization, manufacturing specifications, and storage conditions will be defined in the final approved product specification.

Also known as: AIM-TEST Active Intervention, Microbiome-Targeted Oral Food Supplement, AI-Guided Microbiome-Targeted Nutritional Intervention

Microbiome-targeted oral food supplement

Matched Oral Placebo DIETARY_SUPPLEMENT

A matched placebo administered as one sachet and one capsule once daily for 12 weeks, followed by a 12-week period without study product. The placebo will be matched as closely as feasible to the active intervention in packaging, appearance, weight, taste, odor, mouthfeel, and administration schedule. It will not contain the active prebiotic, postbiotic, botanical, mineral, or other functional ingredients included in the experimental formulation and will be designed not to meaningfully affect testosterone regulation, the gut microbiome, or the principal hormonal and metabolic study outcomes. The final composition and manufacturing specifications will be documented in the approved placebo specification.

Also known as: AIM-TEST Placebo

Matching placebo oral supplement

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants aged 30 to 65 years at the time of informed consent.
• Ability to understand the study, provide written informed consent, and comply with study procedures, including repeated morning blood sampling, completion of validated Turkish patient-reported outcome measures, and collection of stool samples.
• At least one persistent sexual symptom compatible with androgen deficiency for at least 3 months:
• reduced sexual desire or libido;
• reduced spontaneous or morning erections; or
• erectile dysfunction.
• Two fasting, post-sleep morning serum total testosterone measurements obtained on separate days 2 to 7 days apart, between 07:00 and 10:00, with both values at least 6.0 nmol/L and below 12.0 nmol/L.
• Calculated free testosterone below 220 pmol/L, calculated from total testosterone, sex hormone-binding globulin, and albumin using the prespecified Vermeulen equation.
• Serum luteinizing hormone and follicle-stimulating hormone concentrations that are low or inappropriately normal for the degree of testosterone deficiency, with no biochemical evidence of primary testicular failure.
• No identified structural, congenital, infiltrative, or otherwise organic hypothalamic or pituitary disorder and no identified organic primary testicular disorder, based on the prespecified clinical and laboratory evaluation.
• Body weight stable within 5% during the 12 weeks before randomization.
• Any chronic medical condition and its associated medication regimen must be clinically stable for at least 12 weeks before randomization.
• Agreement not to initiate testosterone therapy, fertility-directed hormonal therapy, anabolic-androgenic steroids, non-study testosterone-enhancing supplements, intensive structured weight-loss treatment, weight-loss medication, bariatric intervention, or non-study probiotic, prebiotic, synbiotic, or postbiotic products during the 12-week intervention period.

You may not qualify if:

• Either qualifying total testosterone measurement below 6.0 nmol/L, or clinical or biochemical severity for which delaying standard diagnostic evaluation or established clinical management would be inappropriate.
• Elevated luteinizing hormone or follicle-stimulating hormone concentrations consistent with primary testicular failure.
• Known Klinefelter syndrome, bilateral orchiectomy, clinically significant testicular trauma, testicular torsion with persistent dysfunction, bilateral cryptorchidism, gonadotoxic chemotherapy or radiotherapy, orchitis with testicular failure, or another established organic testicular disorder.
• Known congenital hypogonadotropic hypogonadism or Kallmann syndrome.
• Known pituitary or hypothalamic tumour or other structural lesion; previous pituitary surgery or cranial radiotherapy; infiltrative pituitary disease; multiple pituitary hormone deficiency; or clinically significant traumatic brain injury affecting pituitary function.
• Persistent hyperprolactinaemia requiring investigation or management; unexplained headache or visual-field symptoms; or another clinical indication for pituitary magnetic resonance imaging that has not been adequately evaluated before randomization.
• Clinically important abnormality of prolactin, thyroid-stimulating hormone, free thyroxine, ferritin, transferrin saturation, or another screening test suggesting an untreated reversible or organic cause of hypogonadism.
• Current fertility-directed hormonal therapy, current specialist evaluation for infertility that should not be delayed, or azoospermia or another fertility disorder requiring immediate standard care.
• Use within the previous 6 months of exogenous testosterone, anabolic-androgenic steroids, selective estrogen receptor modulators including clomiphene or enclomiphene, human chorionic gonadotropin, gonadotropins, aromatase inhibitors, dehydroepiandrosterone, or another androgen-active hormonal intervention.
• Current use of a gonadotropin-releasing hormone agonist or antagonist, antiandrogen, chronic opioid therapy, systemic glucocorticoids above physiological replacement, ketoconazole at a dose expected to suppress steroidogenesis, or another medication known to materially suppress or alter the hypothalamic-pituitary-testicular axis.
• Initiation or clinically important dose change within the previous 12 weeks of a medication likely to materially affect sexual function, body weight, glucose metabolism, or testosterone concentrations. Stable background therapy may be permitted when prospectively approved by the investigator and maintained unchanged through Week 12.
• Untreated or inadequately treated moderate-to-severe obstructive sleep apnoea.
• Rotating or night-shift work, severe sleep disruption, or another circumstance that prevents standardized fasting post-sleep testosterone sampling.
• Acute or subacute systemic illness, acute infection, or clinically significant inflammatory flare within 4 weeks before randomization.
• Major surgery within 8 weeks before randomization.

Sponsors & Collaborators

• Varol TUNALI: lead
• Izmir City Hospital: collaborator
• Aydin Adnan Menderes University: collaborator

Study Sites (1)

Aydın Adnan Menderes University

Aydin, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Eunuchism; Hypogonadism; Erectile Dysfunction

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Study Officials

• Varol TUNALI, Dr.

  Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy;

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, care providers, investigators, outcome assessors, central laboratory personnel, and the primary study statistician will remain masked to intervention allocation. The active intervention and placebo will be matched as closely as feasible in packaging, appearance, weight, taste, odor, mouthfeel, and administration schedule. Allocation codes will be maintained by a function independent of clinical operations. Emergency unmasking will be permitted only when knowledge of allocation is required for immediate clinical management. A firewalled unmasked safety statistician and an independent Data and Safety Monitoring Committee may review unmasked safety data but will not participate in efficacy assessments or the primary analysis. Masking integrity will be evaluated at Week 12.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Medical Officer (CMO)

Model Details: Multicenter, randomized, double-masked, placebo-controlled, parallel-group superiority study with two concurrent intervention arms. Participants are assigned in a 1:1 ratio to receive either a fixed-formula, microbiome-targeted nutritional supplement or a matched placebo once daily for 12 weeks, followed by a 12-week intervention-free follow-up period. No crossover occurs. Randomization is stratified by study center, baseline mean total testosterone level (\<8.0 versus ≥8.0 nmol/L), and obesity status (body mass index \<30 versus ≥30 kg/m²).

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 12, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 12, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 12 months after publication of the primary study results and remaining available for 5 years.
• Access Criteria: Access may be granted to qualified researchers who submit a methodologically sound research proposal. Proposals will be reviewed for scientific validity, participant privacy, consistency with the informed consent, and compliance with applicable legal and ethical requirements. Approved researchers must sign a data-use agreement and use the data only for the approved analyses. The agreement will prohibit attempted participant re-identification and unauthorized data redistribution. Data will be transferred through a secure controlled-access mechanism.

Locations

TU (1)