Osteoarthritis of the hand Musculoskeletal Diseases
Conditions
Interventions
The primary research question is whether carrying out a full randomised controlled trial of estrogen-containing therapy in post-menopausal women with symptomatic hand OA is feasible. This is because t
Sponsors
University of Oxford
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 28/02/2020: 1. Able to give informed written consent 2. Female, aged 40-65 years old 3.1. 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 3.2. 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 4. Hand pain, aching or stiffness on most days in the last 3 months 5. At least two painful hand joints of any type (interphalangeal joints (IPJ) or base of thumbs) 6. Fulfils ACR (American College of Rheumatology) clinical diagnostic criteria for hand OA (3 or more of following): 6.1 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) 6.2 Hard tissue enlargement of 2 or more of the DIPJs 6. 3 Less than 3 swollen metacarpophalangeal joints (MCPJ) 6.4 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 7. Hand pain has not responded adequately to NICE 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 8. 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 9. In the Investigator’s opinion, is able and willing to comply with all trial requirements Previous inclusion criteria: 1. Able to give informed written consent 2. Female, aged 40-65 years old 3.1. 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 3.2. In those who have undergone hysterectomy or are 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 (added 11/10/2019) 4. Hand pain, aching or stiffness on most days in the last 3 months and fulfils ACR (American College of Rheumatology) clinical diagnostic criteria for hand OA (3 or more of following): 4.1. 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) 4.2. Hard tissue enlargement o
Exclusion criteria
Exclusion criteria: 1. Other cause of hand pain, including inflammatory arthritis, connective tissue disorder, chronic pain or alternative clinical diagnosis such as tenosynovitis or carpal tunnel syndrome 2. Pregnancy or breastfeeding, or risk of this during study 3. Use of one or more prohibited treatments within specified time frame, or not willing to avoid treatment for the duration of the study: 3.1. Oral contraceptive pill, or systemic HRT within the last 6 months? 3.2. Anti-estrogen medication within the last 6 months 3.3. Oral, intramuscular or intraarticular steroid within the last 3 months 3.4. Intraarticular hyaluronan to a hand joint within the last 6 months 3.5. Initiation of new oral analgesia within last 4 weeks 3.6. Initiation of glucosamine, chondroitin, hand exercises or other relevant non-pharmacological therapy within last 6 weeks 3.7. Hand surgery within the last 6 months, or planned within the next 6 months 3.8. Medications likely to increase hepatic metabolism of study medication, including: 3.8.1. St John’s Wort 3.8.2. Anti-convulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine) 3.8.3. Some anti-infectives (rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and nelfinavir) 4. Presence of one or more medical contraindications to the use of systemic hormonal replacement therapy: 4.1. Any history of breast, endometrial, ovarian or skin cancer 4.2. Any other history of other cancer within 5 years (except treated Basal Cell Carcinoma) 4.3. Relevant breast issue on routine national breast screening in prior 3 years 4.4. Undiagnosed genital bleeding, or untreated endometrial hyperplasia, active uterine fibroids or endometriosis 4.5. 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¥) 4.6. Active or past history of arterial thrombo-embolic disease (such as myocardial infarction, angina or stroke) or strong family history of stroke¥) 4.7. Clinically significant immobility 4.8. Migraine or active epilepsy 4.9. Uncontrolled hypertension (or diastolic pressure greater than 90 mmHg or systolic pressure greater than 145 mmHg at screening visit) 4.10. Uncontrolled diabetes mellitus or uncontrolled hypertriglyceridaemia 4.11. Body Mass Index greater than 30 4.12. Active malabsorption syndrome or clinically significant small bowel disease 4.13. Acute liver disease, clinically significant abnormal liver function, active gallbladder disease or porphyria 4.14. Clinically significant renal impairment 4.15. Intolerance to lactose, fructose or glucose (including galactose intolerance, lactase deficiency, fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency) 4.16.Known sensitivity to either conjugated equine estrogens, bazedoxifene or the combination 5. Any
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility outcome measures: 1. Rates of eligible participant identification: frequency, and relationship to the study medication, recorded throughout the study 2. Rates of recruitment/randomisation from different sources, recorded throughout the study 3. Retention rates, recorded throughout the study 4. Tolerability/adverse events, recorded at weeks 4, 12, 24 and 28 5. Likelihood that participant or Investigator have become unblinded, measured using Bang’s Blinding Index (likelihood of unblinding) self-complete questionnaire at week 24 6. Study medication compliance monitored via diaries at weeks 4, 12 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured at baseline, week 4 (average hand pain and remote pain rating only), week 12 and week 24: 1. Pain and function: 1.1. Average hand pain over last 14 days, measured using NRS 0-to-10, where 0 is “no pain” and 10 is “pain as bad as you can imagine” 1.2. Remote pain-rating (recorded via LimeSurvey, or in paper diary) prior to a visit, NRS 0-to-10, where 0 is “no pain” and 10 is “pain as bad as you can imagine” 1.3. Prevalence of joint pain in other joints in last 4 weeks, measured using pain manikin 1.4. Hand OA-related functional impairment, measured using Functional Index for Hand OA (FIHOA). It includes 10 questions scored according to a 4-grade scale. The score ranges from 0 (no functional impairment) to 30 points (maximal impairment). 1.5. Quality of life measured using EQ-5D-5L. Validated measurement of quality of life across five dimensions and their associated levels of severity on a 1 (no problems) to 5 (extreme problems) scale. 2. Menopause symptoms, measured using: 2.1. The Menopause Specific Quality of Life Questionnaire (MENQOL). Validated measurement of menopausal symptoms and their associated degree of severity; 30 items in a Likert-scale format. Items are rated as present or not present and if present how bothersome, on a 0 (not bothersome) to 6 (extremely bothersome) scale. The interventional version is being used here, which includes an additional 3 questions relevant to HRT use which has been used in a trials setting. 2.2. Greene Climacteric scale. A 21-item validated questionnaire that measures a variety of menopausal symptoms on a 4-point Likert scale (0 = “not at all” to 3 = “extremely”), plus one sexual function probe. 3. Joint appearance, measured using: 3.1. Cosmesis score of Michigan Hand Questionnaire (4 questions, questions 28-31). Subdomain of hand-specific ou | — |
Countries
England, United Kingdom
Outcome results
None listed