Can Vitamin C Reduce the Risk of Postoperative Shoulder Stiffness? A Multi-center, Double-blinded, Randomized and Placebo-controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Difference between the external glenohumeral joint rotations of the operated shoulder and the opposite shoulder
研究概览
简要总结
Postoperative shoulder stiffness is a common complication after shoulder surgery (incidence 10-15%). The symptoms consist primarily in a painful impairment of the mobility of the glenohumeral joint, usually after initially good course. Cause and origin are not clear.
Vitamin C is known as an inactivator of free radicals and plays a key role in building collagen tissue. Vitamin C thus has a modulating role in inflammatory reactions. Injured and ill people have been shown to have significantly increased vitamin C needs, which underlines this role. Evidence was also found that vitamin C has a positive influence on similar diseases such as the complex regional pain syndrome (CRPS, Morbus Sudeck) on the wrist and postoperative arthrofibrosis on the knee joint.
The Investigators want to investigate whether vitamin C intake can positively influence the incidence and / or severity of postoperative shoulder stiffness after shoulder surgery.
The primary objective of this study is to investigate the effect of vitamin C on the external rotational ability of the operated shoulder in the glenohumeral joint compared to the opposite side at 12 weeks post surgery.
Secondary objectives of this study are to investigate other shoulder mobility tests, patient-reported outcomes (level of pain, ability/return to work, smoking habits), patient-reported questionnaires (Constant Score, Oxford shoulder score, DASH score) and the incidence of a frozen shoulder at 6, 12, 26, and 52 weeks post surgery.
Total duration of study: 2.5 years.
详细描述
Participants will be randomly allocated to the two treatment arms, vitamin C or placebo, in a 1:1 ratio Study participants in the verum group receive one capsule of Burgerstein Vitamin C retard 500mg b.i.d. with treatment starting in the evening on the day of the operation for a total of 50 days.
The placebo group receives one placebo capsule b.i.d. with treatment starting in the evening on the day of the operation for a total of 50 days. Vitamin C will be administered orally. Burgerstein Vitamin C Retard Capsules 500 mg (Pharmacode: 6739189) will be used for this study. Active substance: Ascorbic acid (Vitamin C, E 300).
Since a known drug should be tested for a new indication, the exclusion of a bias by a placebo effect, the administration of a placebo to the control group is necessary. To exclude a detection bias and a performance bias, the study is performed double-blind. A randomization protects against a selection bias.
The determination of the sample size is based on the following considerations. The primary endpoint is not expected to be normally distributed. Therefore the sample size determination is based on a Mann-Whitney test for the comparison of the two groups (placebo and treatment) assuming a logistic distribution. Based on a few data of comparable measurements the Investigators think that the standard deviation of the primary endpoint is 10(=SD) in each group. The treatment effect is expected to be Delta=10, a medically reasonable effect.
To achieve a power of at least 80% for the 4 tested comparisons in the final analysis of the primary endpoint, a minimal sample size of 42 in each of the 4 patient groups (strata) is required. In expectation of a drop-out rate of 20%, the target sample size will be 50 patients in each stratum and 200 patients in total, with 100 in the placebo group and 100 in the treatment group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
All study participants and trial personnel but the persons generating the randomization list and preparing the blinded drug packs at the Inselapotheke and Spitalapotheke Lindenhof will be blinded to the assigned treatment. Blinding will be upheld until all analyses are completed. Vitamin C and placebo will be provided in identical looking capsules in drug packs, which will also look identical except for the consecutive code number which is unique on each pack.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent as documented by signature
- •18 years or older at the time of informed consent signature
- •Complication-free rotator cuff* or shoulder arthroscopy** with or without resection of the acromioclavicular joint at the orthopedics Sonnenhof. The rotator cuff operations are basically open or in mini-open technique, usually with additional tenotomy / tenodesis of the long biceps tendon.
- •* rotator cuff surgery can include tenotomy/tenodesis of long biceps tendon, intra-articular debridement with or without resection of the coracoacromial ligament and/or acromioplasty, biopsies, diagnostic arthroscopy
- •** Arthroscopic procedures include subacromial debridement (including partial resection of the coracoacromial ligament & acromioplasty), diagnostic arthroscopy, tenotomy of the long biceps tendon, intra-articular debridement, resection of calcium depots for treatment of tendinitis calcarea, biopsies, stabilizations (only without postoperative immobilization)
- •Sufficient knowledge of German to understand the patient information and informed consent, follow instructions by study personnel, and complete patient questionnaires & diary
排除标准
- •Contraindications to ascorbic acid or one of the excipients, e.g. known hypersensitivity or allergy to the investigational product
- •Planned single or multiple intake of vitamin supplements during the study period, which results in an additional daily intake of > 50 mg ascorbic acid
- •Known pregnancy or breast feeding
- •Known or suspected non-compliance, for example drug or alcohol abuse
- •Inability to follow the procedures of the study, e.g. due to psychological disorders, dementia, etc.
- •Participation in another interventional study within the 30 days preceding and during the present study
- •Previous enrollment into the current study
- •Enrollment of the investigator, his / her family members, employees and other dependent persons
- •Current or previous frozen shoulder (no matter on which side)
- •Pre-surgery on the affected shoulder joint (preoperative procedures include all procedures examined in this study, including all other procedures involving the glenohumeral joint and / or acromioclavicular joint. In addition, all interventions, which as a result, negatively influence the mobility of the shoulder with great likelihood up to the current time)
- •Known current unstable medical problem on the not-affected shoulder joint according to the judgment of the investigator
- •Taking a cortisone preparation or an immunomodulatory drug (for example methotrexate or similar)
- •Alcoholism (defined as intake of more than 12g (women) or 24g (men) alcohol per day)
- •Regular hemodialysis
- •Known diabetes mellitus
- •Known Addison's disease
- •Known not correctly adjusted thyroid metabolism
- •Known Parkinson's disease and similar CNS disorders (Diffuse Lewy Body Disease, Corticobasal Degeneration, Multisystem Atrophy, Progressive Supranuclear Paralysis, Essential Tumor, Huntington's Disease, Multiple Sclerosis)
- •Known diseases / injuries of the peripheral nerves (Isaac's Syndrome, Stiff-Person Syndrome, Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, Hereditary Neuropathies, Amyotrophic Lateral Sclerosis, Hereditary Motor Neuropathies Prone to Pressure Paralysis, Motor Neurone Diseases, Myasthenia Gravis, Spinal Muscular Atrophies, Thoracic Outlet Syndromes)
- •Known infection in the shoulder joint to be operated
- •Known Hyperlipidemia
- •Known Uremia
- •Known Thalassemia
- •Known iron storage diseases
- •Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •Planned further operation of any kind within the next 50 days after shoulder surgery
研究组 & 干预措施
Vitamin C
Patients who are assigned to the experimental treatment group will be given extended release capsules with 500 mg of ascorbic acid orally two times daily, packed in PET/PP-bottles identical as used for the licenced product.
干预措施: Vitamin C (Drug)
Placebo
The control intervention of this study consists of treatment with no active substance (placebo) but in the same schedule as the experimental treatment (verum).
干预措施: Placebo (Drug)
结局指标
主要结局
Difference between the external glenohumeral joint rotations of the operated shoulder and the opposite shoulder
时间窗: 12 weeks post surgery
The primary endpoint of this study is the difference between the external glenohumeral joint rotations of the operated shoulder and the opposite shoulder ("Delta ∆"). The external glenohumeral joint rotation was chosen as primary measure for shoulder performance because this is the component of movement in the shoulder joint, which is the first and most severely impaired in postoperative shoulder stiffness and which normalizes as the last after the symptomatology subsides. Delta ∆ was chosen as an outcome measure, since the standard deviation of the external rotation capability in the population is very high. The external glenohumeral joint rotation of both shoulders is measured using a smartphone with the App "GetMyROM".
次要结局
- Delta ∆ of the external glenohumeral joint rotation(after 6, 26, and 52 weeks post surgery)
- Delta ∆ of abduction(after 6, 26, and 52 weeks post surgery)
- Delta ∆ of internal rotation(after 6, 26, and 52 weeks post surgery)
- Constant Score(preoperatively and depending on the procedure after 6 and 12 weeks (strata 3 & 4), and after 26 and 52 weeks (all strata))
- Delta ∆ of flexion(after 6, 26, and 52 weeks post surgery)
- Level of pain(daily during the first 50 days post surgery, and at 12, 26, and 52 weeks post surgery as a criterion for the occurrence of postoperative frozen shoulder)
- Work ability(6, 26, and 52 weeks post surgery)
- Oxford shoulder score(preoperatively and after 6, 12, 26, and 52 weeks)
- Smoking habits(end of the study, up to 2.5 years)
- DASH score(preoperatively and after 6, 12, 26, and 52 weeks)
- Frozen shoulder(end of the study, up to 2.5 years)