|- candidate number||4340|
|- NTR Number||NTR1525|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-nov-2008|
|- Secondary IDs||PR 3084 |
|- Public Title||Estetrol Therapy in Sjögren’s Syndrome: An Open Proof of Concept |
|- Scientific Title||Protocol for Investigator Initiated Study
Estetrol Therapy in Sjögren’s Syndrome: An Open Proof of Concept |
|- Healt Condition(s) or Problem(s) studied||Sjogren's syndrome, Estetrol|
|- Inclusion criteria||1. Have the capacity to understand and willing to sign an informed consent form. |
2. Fulfill American-European consensus criteria for primary Sjögren’s syndrome.
3. Postmenopausal women ≥ 18 and ≤ 70 years of age at the time of screening.
4. Body mass index ≥18 and ≤32 kg/m2.
5. Have complaints consistent with oral and ocular dryness.
6. The screening laboratory test results must meet the following criteria: SSA and/or SSB positive.
|- Exclusion criteria||1. Have a history of alcohol or substance abuse within the preceding 6 months.|
2. Have a history of malignancy.
3. Have a history of trombo-embolic events or a positive lupus anticoagulant.
4. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
5. Clinically significant abnormal results of routine hematology, serum biochemistry,
urinanalysis, in the opinion of the Investigator at screening, and/or known ECG abnormalities.
6. Known clinically significant abnormal mammogram (presence of any non-cystic mass) within one year before study start.
7. Known clinically significant abnormalities of the uterus and/or ovaries detected earlier by examination and/or ultrasound.
8. A cervical smear with clinically relevant abnormal cytology within one year before study.
9. Previous use of estrogen/progestogen.
10. Use of hormone containing implant at any time.
11. Contraindications for using steroids.
12. Any enzyme affecting drugs from 30 days prior to Day 1 (see Appendix I) and the use of griseofulvin, phenytoin, barbiturates, carbamazepine, rimfampicin, nelfinavir, ritonavir, ketonazole, primidone, oxcarbazepine, topiramate, felbamate, herbal remedies containing hypericum perforatum (St. John’s wort).
13. Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
14. Use of any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||13-nov-2008|
|- planned closingdate||26-mrt-2009|
|- Target number of participants||10|
|- Interventions||20 mg estetrol per day during 28 days|
|- Primary outcome||Primary endpoint consists of a composite endpoint concerning meaningful improvement across 2 or 3 Sjögren’s syndrome disease domains: oral, ocular and laboratory test|
|- Secondary outcome||Secondary endpoints include: |
- improvement in quantitative levels of SSA and/or SSB
- decrease in pilocarpine use during treatment
- improvement in results of SF36
|- Timepoints||November/December - recruitment|
First patient in: November 2008
Last patient out: March 2009
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||Drs. S.A.M. Ennecker-Jans|
|- CONTACT for SCIENTIFIC QUERIES||Drs. S.A.M. Ennecker-Jans|
|- Sponsor/Initiator ||Erasmus Medical Center, Rotterdam|
(Source(s) of Monetary or Material Support)
|- Brief summary||Design: |
An open, proof-of-concept, investigator initiated study
Female postmenopausal patients with primary Sjögren’s syndrome and complaints; no contraindications for estrogens especially no increased risk and/or history of thrombo-embolic events
Estetrol, dose of 20 mg per day during 28 days.
first 4 weeks run-in period with placebo, thereafter 4 weeks treatment with estetrol, followed by 14 days treatment with a progestogen.
Phase II (proof-of-concept)
To explore overall response to treatment with estetrol in patients with primary Sjögren’s syndrome.
· improvement in quantitative levels of SSA and/or SSB
· decrease in pilocarpine use during treatment.
· improvement in results of the SF36
· safety of estetrol treatment.
Primary endpoint consists of a composite endpoint concerning meaningful improvement across 2 of 3 Sjögren’s syndrome disease domains: oral, ocular, and laboratory tests.
· Oral improvement will be defined as ≥20% in the patient’s assessment of dry eyes (on a 100 mm VAS) or ≥20% improvement in total unstimulated salivary flow.
· Ocular improvement will be defined as ≥20% improvement in either the patient’s assessment of dry eyes by VAS or the results of the Schirmer’s test without anaesthetic.
· Laboratory improvement will be defined as ≥20% improvement in the serum IgG or the ESR.
|- Main changes (audit trail)|
|- RECORD||6-nov-2008 - 4-jun-2011|