This trial is active, not recruiting.

Condition sjogren's syndrome
Treatment dehydroepiandrosterone
Phase phase 4
Sponsor Helsinki University
Collaborator Göteborg University
Start date February 2003
End date December 2009
Trial size 107 participants
Trial identifier NCT00543166, T101090002


Our research contributes to the understanding of some of the basic biology of the salivary glands. The etiology and many of the pathomechanisms of Sjögren's syndrome are unknown. In particular, reasons for the female dominance, late age of onset, fatigue and the prominent involvement of exocrine glands are unknown. We hypothesize, due to the disease characteristics, that the primary target hit by the disease process is the secretory acinar cell and that this cell is particularly damaged in women due to insufficient support, normally provided by dehydroepiandrosterone and its intracrine processing.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
(Placebo Comparator)
180 patients divided to two separate groups (each containing 90 patients). This study has a cross-over, wash-out design, which consists of two 4 month treatment period separated by a one month long wash-out period. During one treatment period the patient gets placebo and during one of the treatment periods the patient gets 50mg of dehydroepiandrosterone (DHEA) in the morning.
dehydroepiandrosterone DHEA
50 mg of dehydroepiandrosterone in the morning for 4 months in the treatment group.

Primary Outcomes

time frame: prospective

Secondary Outcomes

Quality of life
time frame: prospective

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: 1. Primary SS according to the American-European consensus criteria 2. General Fatigue ≥14 calculated from MFI-20 (Multiple fatigue inventory-20 questionnaire; the value was based on a pilot study of 239 members of the Finnish SS patient association) 3. subnormal serum S-DHEAS values (the reference values were calculated based on a pilot study of 81 healthy women and 57 healthy men). Exclusion Criteria: 1. Age <18 years or >80 years 2. prisoner 3. individuals not able to give their informed consent 4. history of breast cancer 5. history of uterus cancer 6. history of prostatic cancer 7. history of stroke or prothrombotic coagulation disorders 8. pregnant or lactating women 9. fertile patients without adequate prevention 10. difficult acne 11. a significant liver disease 12. patients with changes in their systemic medication taken for SS during the previous three months 13) patients taking more than 10 mg prednisolone per day

Additional Information

Official title Sex Steroids in Sjögren's Syndrome: Effect of Substitution Treatment on Fatigue
Principal investigator Yrjö Konttinen, MD, PhD
Description We hypothesize, due to the Sjögren's syndrome (SS) disease characteristics, that the primary target hit by the disease process is the secretory acinar cell and that this cell is particularly in women damaged due to insufficient support, normally provided by dehydroepiandrosterone and its intracrine processing. Dehydroepiandrosterone deficiency at the time of adrenopause seems to us as the more likely endocrine trigger than estrogen deficiency caused by menopause as androgens in general are considered to be protective against autoimmunity and estrogens to favor it. Acinar cell is normally responsible for the production of primary saliva. Acinar cell damage can lead to acinar cell apoptosis and loss. Normally this is compensated by division of the acinar cells in situ or, according to recent reports, perhaps rather by division and subsequent migration of one of the daughter cells into the acinar space and transdifferentiation of this intercalated ductal cell progenitor into mature acinar cell. In SS this remodeling seems to be impaired, perhaps for the same reason, which also leads to primary acinar cell damage. According to this hypothesis, the primary changes occur in the salivary glands and more specifically in the acinar cells, whereas immune activation and autoimmunity are secondarily activated against abnormally damaged acinar cells so that individuals with the "right" genetic background also produce SS-A and SS-B antibodies. The cause of the acinar cell damage may not be a direct, damaging stimulus, e.g. virus infection or irradiation damage, but rather lack of a supporting anabolic stimulus and inadequate maintenance of the acinar cell health leading to cytopathic acinar cell changes. In peri-menopausal women (who still produce some estrogens) this abnormal antigen release and processing from acinar cells, which reveals cryptic epitopes, together with autoimmunity enhancing effects of estrogens, may lead to the full picture of SS (Cutolo et al., 2004). This neuroimmunoendocrine working hypothesis would explain many central disease characteristics, but does not provide a final answer to the mystery of this intriguing syndrome as the reasons for the insufficient production and generation of DHEA remain to be solved. We have done some preliminary studies to analyze this topic by mapping the signals of the extracellular matrix in the adrenal cortex, where the cells proliferate in the outer zone and subsequently migrate in a centripetal direction, during which phenotypic transition occurs from the outer zone (zona glomerulosa) cells producing aldosterone to the intermediate zone (zona fasciculata) cells producing glucocorticosteroids and finally to the inner zone (zona reticularis) cells producing DHEA. However, in this research project we have decided to totally focus on the salivary gland acinar cell-sex steroid interactions.
Trial information was received from ClinicalTrials.gov and was last updated in November 2007.
Information provided to ClinicalTrials.gov by Helsinki University.