Double Blind Placebo-controlled RCT of the Efficacy and Safety of Intramuscular Injections of Botulinum Toxin A as a Treatment for Provoked Vestibulodynia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Self-reported dyspareunia measured by VAS
研究概览
简要总结
Women with provoked vestibulodynia (PVD) suffer from severe dyspareunia and often present a hyperactivity of the pelvic floor muscles (PFM) which maintain the dyspareunia. The rationale for the study is that for women with PVD who don't succeed to restore the function of the PFM by physiotherapy, Botulinum Toxin A (BTA) could be an optional treatment by decreasing the high muscle tonus and thus possibly reduce the coital pain.
详细描述
Design and methodology General outline The study is an investigator- initiated phase III study to determine the effect of botulinum toxin A injections in the bulbocavernosus muscles in women with provoked vestibulodynia for reduction of the level of dyspareunia. The study will be a double blind, placebo-controlled RCT analyzed according to the intention to treat. The study will be carried out according the trial protocol, current regulations (LVFS 2011:19, ICH GCP) and to the latest version of the Helsinki declaration. Ethical approval from the Stockholm regional ethic committee will also be obtained before the study begins. No financial support from the manufacturer of the active drug is obtained.
Women with PVD, age 18-40 years, will be informed about the study by their gynecologist or via advertisement with information on how to contact the research nurse or the responsible gynecologists for more information. If the diagnosis of PVD needs to be clarified, a screening appointment will be scheduled.
It is estimated that the project will require 4 years for recruitment and treatment of all participants, follow-ups, data analyses and report of results.
During the recruitment, the patients with PVD will be asked to participate in an epigenetic study analyzing the grade of methylation of certain candidate genes associated to pain and anxiety before and after treatment and a "genome wide association study" with the aim to find possible genetic markers of PVD. If they accept, a venous blood sample will be taken during Visit 1 and Visit 5. These studies are otherwise separated from the RCT and have ethical approval. The blood samples will be registered in Stockholms Medicinska Biobank (registreringsnummer 941 hos IVO) and stored for later analyses at the research department of Dept. of Obstetrics and Gynecology, 182 88 Danderyd, Sweden.
Visit 1(recruitment and baseline) If the patient is willing to participate and fulfill inclusion and exclusion criteria she will sign informed consent in the presence of the gynecologist in charge of the injections of BTA or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age 18-40 years
- •PVD defined as significant pain at vestibular contact and vaginal entry (VAS ≥ 6 at the tampon test or severe pain, preventing intercourse)
- •Duration of symptoms of ≥ 3 months,
- •Patients who are willing to participate in the study after it has been explained orally and in writing will be included.
排除标准
- •Vulvo-vaginal infection, dermatological conditions or other causes to dyspareunia
- •Regular medication with analgesics
- •Major psychiatric or medical disease
- •Known allergy to any components of the active drug (Botox®) or medical disease contradictory to treatment with the active drug (Botox®) (peripheral motor neurological disease such as myasthenia gravis, amyotrophic lateral sclerosis or Lambert-Eaton syndrome and diabetes),
- •Pregnancy - a pregnancy test will be taken before both treatments (Visit 1 and 3), unless the participants are using highly effective birth control methods that can achieve a failure rate of less than 1% per year, when used consistently and correctly. Such methods include;
- •combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- •progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- •intrauterine device (IUD)
- •intrauterine hormone-releasing system (IUS)
- •bilateral tubal occlusion
- •sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject.
- •Pelvic floor deficiency with urine and or flatulence incontinence.
研究组 & 干预措施
Botulinum Toxin Type A
50 Allergan units (0.5 ml) injected in m bulbocavernosus twice with 3 months in between treatments
干预措施: Botulinum Toxin Type A (Drug)
Sterile saline solution
0.5 ml of sterile saline injected in m bulbocavernosus twice with 3 months in between treatments
干预措施: Sterile Saline Solution (Drug)
结局指标
主要结局
Self-reported dyspareunia measured by VAS
时间窗: Baseline to 6 months after baseline
VAS 0 (no pain) to 100 (worst pain imaginable)
次要结局
- Pain at tampon insertion measured by VAS 0-100(Baseline to 6 months after baseline)
- Quality of Life (questionnaires)(Baseline to 6 months after baseline)
- Reduction of pelvic floor hyperactivity/tonus,(Baseline to 6 months after baseline)
- Psychosexual evaluations (questionnaires)(Baseline to 6 months after baseline)
- Registrations of adverse events(1 year)
研究者
Nina Bohm-Starke
Associate professor
Karolinska Institutet