Overview

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

Status:
Active, not recruiting
Trial end date:
2021-12-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
N/A
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Oxford
Collaborators:
National Institute for Health Research, United Kingdom
Oxford Clinical Trials Research Unit
Treatments:
Bazedoxifene
Estrogens
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