Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial

• Status: Completed
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: Male

Summary

Today, it is evident that vitamin D (VD) has more widespread effects than the classical actions related to bone mineralization and calcium homeostasis1. VD deficiency results in impaired reproductive performance in various species of animals, and recently the investigators have shown that the VD receptor (VDR), activating (CYP2R1, CYP27A1, CYP27B1) and inactivating (CYP24A1) enzymes are expressed in the human testis, epididymis, seminal vesicle, prostate and spermatozoa. Our following functional studies showed that VD increases intracellular calcium in mature spermatozoa, and hence may be important not only for spermatogenesis but also for sperm maturation. A new, and yet unpublished cross sectional study of 300 young healthy Danish men showed that men with lower levels of serum VD have significantly lower number of normally developed and motile spermatozoa. Hitherto, most cases of male infertility have been classified as "idiopathic", and infertile couples have been referred to symptomatic treatment at infertility clinics. These fertility treatments are often physically demanding for the female partner as well as expensive for the health care system. Any treatment that might improve semen quality of involuntary infertile men would be beneficial both for the infertile couples and the society in general. Our findings that VD may play a role for human semen quality have not yet been tested clinically. However, if VD supplementation proves efficient this opens for the first time for a causal, safe and cheap treatment of at least some cases of "idiopathic" impaired semen quality. The investigators believe our new human data supported by the results from the VD deficient and VDR KO animal studies and the high proportion of VD deficient Danish men provide sufficient evidence to initiate a randomized clinical trial of VD supplementation to infertile men. Infertile men have also have unfavorable altered levels of sex hormones and higher mortality than fertile men. Since VD deficiency is associated with increased mortality, regulation of aromatase, immune system, bone metabolism, glucose metabolism, cardiovascular system etc. our suggested clinical trial may also be able to evaluate several secondary endpoints in addition to the potential effect on semen quality.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rigshospitalet, Denmark
• Treatments: Calcium; Calcium, Dietary; Cholecalciferol; Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

• Male with an age > 18 years old

• Referred for male infertility with sperm concentration >= 0.01 million/ml. Additionally, all men must have either sperm concentration < 20 million/ml or < 50% progressive motile spermatozoa or < 12% morphological normal spermatozoa using strict criteria

Exclusion Criteria:

• Men with chronic diseases (such as diabetes mellitus, Thyroid disease, endocrine disturbances in need of treatment, malignant disease, or diseases known to interfere with VD intake or very sensitive to VD intake (such as inflammatory disease with granuloma: sarcoidoses, tuberculosis, Wegeners, vasculitis, inflammatory bowel disease (Crohn's and colitis ulcerosa etc).

• Men with present or previous malignant disease

• If there is an indication for testis biopsy and it is planned or conducted within the next 6 months

• Serum 25-hydroxy-D3 > 50 nmol/l at the time of inclusion

• Serum Calcium ion > 1,35 mmol/l

• Inhibin-B < 30 pg/ml

• Intake of vitamin D above 15 ug daily

• Allergy towards vitamin D or arachidis oil (peanuts)

• Men with total or partly obstructive oligospermia and men who had vasectomy performed

Criteria for drop out:

• Abrogation of the treatment

• Newly diagnosed endocrine, calcium metabolic disease, parathyroid, thyroid, diabetes or other endocrine disease in need of treatment

• New malignant disease

• Treatment with chemotherapy, immunomodulating therapy, salazopyrin

• Oral or iv treatment with steroid hormones

• Treatment with diuretics, antihypertensive treatment, treatment the heart, calcium channel blockers

• Development of vitamin d intoxication

• If testis biopsy is performed or other surgery in the genital region during the trial