Can we Use Estrogen-containing Therapy to Improve Pain in Women After Menopause With Hand Osteoarthritis?

NCT ID: NCT04036929

Last Updated: 2022-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-09
• Study Completion Date: 2021-12-10

Brief Summary

Post-menopausal women aged 40-65 with symptomatic hand osteoarthritis are invited to take part in this feasibility study. The study's aim is to investigate whether it is acceptable to women with painful hand OA to take an estrogen-containing therapy, and what is the best way of collecting some of the information in order to facilitate planning a full size trial. The investigator's long-term aim is to find out whether giving estrogen-containing therapy to women after the menopause improves hand OA symptoms.

Conditions

Hand Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Estrogen-bazedoxifene

Tablet, once daily for 6 months.

Group Type: EXPERIMENTAL

Estrogen-bazedoxifene

Intervention Type: DRUG

Conjugated estrogens 0.45 mg-bazedoxifene acetate 20 mg.

Placebo

Closely matched tablet, once daily for 6 months.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Placebo oral tablet

Interventions

Estrogen-bazedoxifene

Conjugated estrogens 0.45 mg-bazedoxifene acetate 20 mg.

Intervention Type: DRUG

Placebo oral tablet

Placebo oral tablet

Intervention Type: DRUG

Other Intervention Names

Duavive

Eligibility Criteria

Inclusion Criteria

• Able to give informed written consent
• Female, aged 40-65 years old
• In those with an intact uterus: At least 12 months of spontaneous amenorrhea (without any menstrual bleeding in last 12 months) and last menstrual period not more than 10 years ago
• In those who have undergone hysterectomy or are/were using an intrauterine contraceptive device with progesterone local therapy (such as Mirena): Follicle stimulating hormone (FSH) ≥30 milli-International Units per millilitre (mIU/ml) on screening blood test AND a history of menopausal symptoms in the last 1 to 10 years, in keeping with appropriate timing of menopausal status
• Hand pain, aching or stiffness on most days in the last 3 months
• At least 2, painful hand joints of any type (interphalangeal joints (IPJ) or base of thumbs)
• Fulfils American College of Rheumatology clinical diagnostic criteria for hand OA (3 or more of following):

1. Hard tissue enlargement of 2 or more of the following joints: 2nd or 3rd distal interphalangeal joints (DIPJ), 2nd or 3rd proximal interphalangeal joints (PIPJ), first carpometacarpal joints (CMCJ)

2. Hard tissue enlargement of 2 or more of the DIPJs

3. Less than 3 swollen metacarpophalangeal joints (MCPJ)

4. Deformity of at least one of the joints listed in first point

OR, for those with base of thumb osteoarthritis only not fulfilling these criteria, has clinical symptoms and examination findings consistent with base of thumb osteoarthritis.

• Hand pain has not responded adequately to National Institute for Health and Care Excellence core guidance for management of OA, including the use of paracetamol or non-steroidal anti-inflammatory drug (NSAID) gel, except where there is contraindication or intolerance
• Average hand pain is reported as typically more than 4 out of 10 in severity, or average hand pain in the last 7 days of 4/10 or more on a visual analogue scale
• In the Investigator's opinion, is able and willing to comply with all study requirements

Exclusion Criteria

• Other cause of hand pain, including inflammatory arthritis, connective tissue disorder, chronic pain or alternative clinical diagnosis such as tenosynovitis or carpal tunnel syndrome
• Pregnancy or breast feeding, or risk of this during study
• Use of one or more prohibited treatments within specified timeframe, or not willing to avoid treatment for the duration of the study:

• Oral contraceptive pill, or systemic HRT within the last 6 months (Use of an intrauterine contraceptive device with progesterone local therapy (Mirena) or vaginal topical estrogen use (known low systemic absorption) are not exclusions to participation)
• Anti-estrogen medication within the last 6 months
• Oral, intramuscular or intraarticular steroid within the last 3 months
• Intraarticular hyaluronan to a hand joint within the last 6 months
• Initiation of new oral analgesia within the last 4 weeks
• Initiation of glucosamine, chondroitin, hand exercises or other relevant non- pharmacological therapy within the last 6 weeks
• Hand surgery within the last 6 months, or planned within the next 6 months
• Medications likely to increase hepatic metabolism of study medication, including:
• St. John's Wort
• Anti-convulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine)
• Some anti-infectives (rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and nelfinavir)
• Presence of one or more medical contraindications to the use of systemic hormonal replacement therapy:

• In those aged 40-45 years, FSH <30 mIU/ml on screening blood test, i.e. non- confirmatory of menopausal status
• Any history of breast, endometrial, ovarian or skin cancer
• Any other history of other cancer within 5 years (except treated Basal Cell Carcinoma, BCC)
• Relevant breast issue on routine national breast screening in prior 3 years
• Undiagnosed genital bleeding, or untreated endometrial hyperplasia, active uterine fibroids or endometriosis
• Active or past history of venous thromboembolism (VTE) (including deep venous thrombosis, pulmonary embolism and retinal vein thrombosis), or at high risk of VTE (such as known thrombophilic disorders (such as Protein C, S or anti-thrombin deficiency) or presence of a strong family history of VTE). Women with a first degree relative with a history of VTE, or other strong family history of VTE at the Investigators' discretion.
• Active or past history of arterial thrombo-embolic disease (such as myocardial infarction, angina or stroke) or strong family history of stroke)
• Clinically significant immobility
• Migraine or active epilepsy
• Uncontrolled hypertension (or diastolic pressure greater than 90 mmHg or systolic pressure greater than 145 mmHg at screening visit)
• Uncontrolled diabetes mellitus or uncontrolled hypertriglyceridaemia
• Body Mass Index (BMI) greater than 30
• Active malabsorption syndrome or clinically significant small bowel disease
• Acute liver disease, clinically significant abnormal liver function, active gallbladder disease or porphyria
• Clinically significant renal impairment
• Intolerance to lactose, fructose or glucose (including galactose intolerance, lactase deficiency, fructose intolerance, glucose-galactose malabsorption or sucrase- isomaltase insufficiency)
• Known sensitivity to either conjugated equine estrogens, bazedoxifene or the combination
• Any other significant or uncontrolled disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study
• Participants who have participated in another research trial involving an investigational product in the past 8 weeks

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Oxford Clinical Trials Research Unit

UNKNOWN

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

White Horse Medical Practice, Faringdon Medical Centre

Faringdon, Oxfordshire, United Kingdom

Charing Cross Hospital, Imperial College Healthcare NHS Trust

London, , United Kingdom

Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Countries

United Kingdom

References

Marian IR, Goff M, Williams JAE, Gulati M, Chester-Jones M, Francis A, Watson M, Vincent TL, Woollacott S, Mackworth-Young C, Glover V, Furniss D, Gardiner M, Lamb SE, Vincent K, Barber VS, Black J, Dutton SJ, Watt FE. Hand Osteoarthritis: investigating Pain Effects of estrogen-containing therapy (HOPE-e): a protocol for a feasibility randomised placebo-controlled trial. Pilot Feasibility Stud. 2021 Jun 24;7(1):133. doi: 10.1186/s40814-021-00869-1.

Reference Type: BACKGROUND

PMID: 34167594 (View on PubMed)

Related Links

https://hope.octru.ox.ac.uk/

HOPE-e study website

Other Identifiers

HOPE-e

Identifier Type: -

Identifier Source: org_study_id