Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hot Flashes

Ovarian Cancer

Ovarian Epithelial Cancer

All participants in the intervention and control group receive the care as usual. The care as usual consists of a clinic appointment with the research nurse. In this appointment the RRSO-induced menopausal complaints will be discussed in more detail. Depending on the complaints at hand, information, reassurance and life style advice will be offered. A leaflet with relevant information will be provided for. Furthermore, the usual medical care may include prescription of (non-)hormonal medicationsTwelve weeks after the clinic appointment, the research nurse will contact all participants per telephone to ask whether there are issues that remain to be addressed.

Participants are allowed to continue the use of all their current medication.

Mindfulness based stress reduction (MBSR) is a standardized eight-week psychosocial intervention delivered by certified trainers. The programme consists of a weekly class of two and half hours for a period of eight weeks and a full retreat day. Furthermore participants are asked to practice exercises at home for 45 minutes, six days a week. The MBSR class will consist of ten to twelve persons, starting at different weekdays and moments of the day. If during the inclusion process it becomes apparent that a group of participants (provided a sufficient group size) comes from a region (e.g. Friesland or Overijssel) with a considerable amount of traveling time to the UMCG, efforts will be made to start a MBSR training in the region with trainers from the UMCG.

Mindfulness based stress reduction (MBSR)

Marian JE Mourits, prof. dr.

Short Rationale: Risk-reducing salpingo-oophorectomy (RRSO) is a mainstay in preventing ovarian cancer in BRCA1/2 mutation carriers, as ovarian cancer screening is ineffective in detecting ovarian cancer in an early and curable stage. Women who underwent RRSO experienced bothersome menopausal symptoms and worsening of sexual functioning related to acute surgical menopause. Hormone replacement therapy (HRT) will mitigate some of the RRSO induced menopausal complaints, however it does not reduce the complaints to a premenopausal level and the sexual symptoms are not alleviated. Mindfulness interventions were found to improve sexual functioning and alleviate menopausal symptoms in various populations. It has not been investigated whether mindfulness-based stress reduction (MBSR) is effective in mitigating the RRSO-induced menopausal complaints in BRCA1/2 mutation carriers and if this effect is sustained over a longer period of time.

Objective: To examine the effect of MBSR training on the menopause-specific quality of life in BRCA1/2 mutation carriers who experience RRSO-induced menopausal complaints.

Study population: Female BRCA1/2 mutation carriers who were younger than 52 years at the time of RRSO reporting two or more moderate to severe menopause related complaints after undergoing RRSO.

Study design: Prospective randomized controlled trial with a follow-up time of twelve months conducted at the University Medical Center Groningen (UMCG)

Intervention: Eight-week MBSR training consisting of a weekly class of two and half hours and a full retreat day. Furthermore participants are asked to practice mindfulness exercises at home for 45 minutes, six days a week.

Main study parameters/endpoints: Menopause specific quality of life score measured by the Menopause-specific quality of life questionnaire (MENQOL). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no risks associated with taking part in a MBSR training or filling out the questionnaires that will be used in this study. The content of the questionnaires concerns intimate matters and could be considered burdensome. A possible benefit for the participants of the MBSR training is that participants will be more able to cope with their complaints after RRSO. The group relatedness is reflected in the fact that RRSO is specifically performed in women with a hereditary risk of ovarian cancer such as BRCA1/2 mutation carriers.

OBJECTIVES This study will evaluate the effectiveness of a mindfulness-based intervention in alleviating RRSO-induced menopausal complaints in BRCA1/2 mutation carriers. The intervention to be tested is MBSR training. The investigators hypothesize that women in the MBSR group will report statistically significantly greater improvement of menopause-specific quality of life from baseline to twelve weeks when compared to the control group and that this improvement will be maintained at six months and twelve months. The investigators also hypothesize that women in the MBSR group will report a statistically significantly greater improvement in sexual functioning and a decrease in sexual distress from baseline to twelve weeks when compared to the control group and that this improvement will be maintained at six and twelve months.

The primary objective is to examine the effect of MBSR training on the menopause-specific quality of life in BRCA1/2 mutation carriers who experience RRSO-induced menopausal complaints.

The secondary objective is to examine the effect of MBSR training on sexual functioning and distress in BRCA1/2 mutation carriers who experience RRSO-induced menopausal complaints.

STUDY DESIGN The study is a prospective, randomized controlled trial, with an intervention group that receives an eight-week MBSR training as well as care as usual and a control group that only receives care as usual. All participants will be asked to fill out questionnaires regarding menopausal and sexual complaints at baseline before randomization (T0) and at twelve weeks (T1), six (T2) and twelve months (T3) after randomization. The study will be conducted at the family cancer clinic of the UMCG.

STATISTICAL ANALYSIS The two treatment arms will be summarized at baseline with frequencies for categorical variables and means, ranges and SDs for continuous variables. Scores for the MenQOL, FSFI and FSDS will be calculated according to published scoring algorithms.

A linear mixed effects analysis will be performed on the relationship between the MenQOL score and the intervention. The scores on the MenQOL at 12 weeks, 6 months and 12 months will be modelled as a function of treatment arm, time moment, their interaction. An unstructured correlation matrix will be assumed, unless the data indicate the presence of another correlation structure. If the groups are unbalanced, covariates will added to the model. All analysis will be conducted on an intention-to-treat basis. All analyses will be performed with SPSS.

Similar analyses will be conducted for the FSFI and FSDS, which will be used as a secondary outcome measure.

Psychosexual Consequences of Risk-reducing Salpingo-oophorectomy

PURSUE - Psychosexual Consequences of Risk-reducing Salpingooophorectomy in BRCA1/2 Mutation Carriers

The MENQOL is a self-administered 29-item questionnaire developed to assess quality of life in menopausal women. It not only records menopausal symptoms, but also the degree of bother women experience due to the menopausal symptoms. It consists of four domains: vasomotor (three items), psychosocial (seven items), physical (sixteen items) and sexual (three items). All items firstly ask whether or not a woman has experienced the item in the prior four weeks. If this was the case she is then asked to indicate how much she was bothered on a zero (no bother) to seven (extreme bother) scale. Higher scores on the MENQOL reflect a poorer menopause-specific quality of life. The minimal clinically important difference was found to be 1.0. The MENQOL is available in Dutch and has undergone extensive linguistic validation.

FSFI is a self-report questionnaire widely used to assess sexual functioning. It consists of nineteen items and the following six sub-domains: desire (items 1 and 2), arousal (items 3-6), lubrication (items 7-10), orgasm (items 11-13), satisfaction (items 14-16) and pain (items 17-19). Each domain can be scored from zero to five on a Likert-type scale. The higher the scores are the better the sexual functioning has been in the prior four weeks. As a clinical cutoff score for sexual dysfunction 26.55 is used. The FSFI is available in Dutch and has undergone extensive linguistic validation

The FSDS is a self-report questionnaire that is used to assess sexual activity related distress in four weeks prior to adminstration. The FSDS consists of twelve items and can be scored on a five point Likert-type scale from zero to four and has a maximum total score of 48. A score of fifteen or higher is the cutoff score for clinically significant distress. The FSDS is available in Dutch and has undergone extensive linguistic validation

University Medical Center Groningen

MD/PhD candidate

Behaviors and Mental Disorders

Skin and Connective Tissue Diseases

Anxiety Disorders

Depressive Disorder

Breast Neoplasms

Depression

Alcohol Drinking

Breast Diseases

Skin Diseases

Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Ethanol

MBSR including brief information session and assessments

MBSR is an 8-week course covering a total of 24 contact hours where the group of patients meet with an clinical psychologist certified as mindfulness instructor. The group will train the ability of mindfulness by specific awareness improving practises (body-scan) guided meditations and soft yoga. Between group-sessions participants are recommended to practice 45 minutes daily and to go through instructions in MBSR hand-outs. Participants will be given audio-CDs containing instructions and guides to support home practice.

mindfulness based stress reduction (MBSR)

Christoffer Johansen, M.D., Ph.D.

The number of Danish women treated for breast cancer rise every year, though survival rates have improved, women can still expect to experience the diverse late effects reported by this group of patients. Mindfulness labels the ability to be aware of the present moment - thereby avoiding speculations about both past and present. Mindfulness based stress-reduction (MBSR) is an 8-week program, covering 24 contact-hours and 45 minutes daily home practice. The program aims at developing participants' coping resources and developing participants' mindful awareness. Thus the program consists of guided meditations, guided body scan(a specific awareness exercise)and through meditation, yoga and psychoeducation concerning stress and stress-reactions, while meditation and bodyscan is practiced at home by the use of specific audio-CDs guiding the patient. The MBSR-program have shoved promising results among patients with anxiety-disorders, depression and chronic pain. Smaller studies have also found positive effects of the program among cancer patients. The investigators want to evaluate the effect of the MBSR program on levels of anxiety and depression as well as the possible influence of mindfulness training on health behaviors and existential concerns. The study are based on the following hypotheses:

* report of anxiety and depression will decrease among cases
* better compliance will lead to more decrease in levels of anxiety and depression
* cases will make lifestyle changes suitable with recommendations for BC patients in post-treatment phase of the illness
* decreased level of anxiety and depression will reflect improved spiritual well-being
* improved spiritual wellbeing will lead to decreased report of physical symptoms

All participants in this randomized controlled trial will fill out questionnaires at enrollment and as 1, 6 and 12 months follow-up. Based on results from this trial clinicians and patients will be able to make decisions regarding post-treatment psychosocial intervention and researchers will have initial evidence of the effect of the intervention and thus possible indications for research on mindfulness among patients diagnosed with cancer at other stages or sites.

Original Research Protocol, Copenhagen January 2007 Cancer and Mindfulness: A prospective, randomized trial of a psychosocial intervention among women operated for breast cancer

Background From the time of diagnosis cancer patients have a need for psychological support. Many patients handle the situation by the help of friends and family, while others need professional support to come to terms with different phases of life as a cancer patient. Only few randomized trials have been conducted in order to determine what kinds of professional support patients will benefit from. These studies conclude that the prevalence of anxiety and depression in reduced. This is of major importance as depending of cancer type, treatment modality, age and gender, a total of 10-50 % of Danish cancer patients reports such well-defined psychosocial symptoms following the diagnosis of cancer.

Mindfulness meditation aims to increase the experience of presence and an increased relation to several emotional and sensory experiences. Instead of being a technique aimed to control and change unwanted psychological states the method is rather a way to stay present in the here and now without judging and as such it has been developed into a stress reduction method: mindfulness based stress reduction (MBSR). The method is taught within a group setting by an instructor guiding the patients during a week long program. The method has been evaluated within a variety of settings and has been found to effectively reduce symptoms related to different stress and pain conditions i.e. psoriasis, chronic pain, HIV/AIDS, anxiety and depression.2 Based on these experiences several programs have been developed and the program developed by Williams and Kabatt-Zinn has gained status as the most commonly applied and best validated. Within recent years the program has been included into cognitive-behavioral therapy. But with potential effects not only as reduction of symptoms but further opens the opportunity for participants to approach spiritual and existential themes. The potential effect is therefore not limited to simple reduction of symptoms but includes increased meaningfulness, quality of life and sense of coherence.

Nine studies of the effect of MBSR haw been conducted, including 10- 157 adult cancer patients being taught MBSR in groups of mainly breast cancer patients, but only three of these trials have been conducted as randomized controlled trials. I these trials patients have self-referred (selection bias), analysis have not been adjusted for biological status of the cancer disease (confounding), samples have been small (n=10-157) (type 2 error) and patients have differed with regard to time since diagnosis (misclassification). Despite these methodological limitations a tendency of positive effects of MBSR participation on psychological and physiological outcomes has been observed.

Yet it is still not determined whether MBSR will provide cancer patients benefit improving their daily life with cancer. Some important aspects have not been addressed in previous studies: When MBSR is applied as an intervention dose-response relation has only been observed among patients with a moderate level of symptoms. Thus sensitivity of MBSR in relation to stages of cancer, levels of pain or negative effects of treatments. We still do not know whether all cancer patients will profit from this type of intervention. Further the influence of patient compliance and working alliance is still not explored.

The diagnosis of cancer accentuates existential dimensions as spirituality and quality of life. Yet we do not know how MBSR can support patients in dealing with such themes. Be review of literature regarding patients coping with cancer the patients demand for interventions supporting their need to deal with existential themes is striking.

Aim We will conduct a randomized controlled trial among women diagnosed with primary breast cancer in order to evaluate the effect of MBSR on depression, anxiety quality of life, health behavior and psychological well-being.

Research questions

* We do not know whether all types of cancer patients will benefit from MBSR. Especially patients compliance must be empirically documented
* Cancer accentuates an array of existential concerns and the effect of MBSR on these subjective concerns must be examined

Inclusion All patient diagnosed with primary breast cancer in Department of Breast Surgery, Copenhagen Hospital Herlev, will be invited to participate in the study and in the randomization allocating patients to either MBSR intervention or treatment as usual control. Patients diagnosed and in active treatment for major psychiatric disease, patients with musculoskeletal disease and cardiovascular disease hindering MBSR participation, and patients previously diagnosed with other cancers than non-melanoma skin cancer will be excluded. A project nurse will contact eligible patients, deliver oral and written information and collect informed consent. If the patient consents baseline questionnaire will be administered.

Randomization will then take place. The project nurse will up-load patient data on secured project home-page. Computer generated sequence will automatically assign a unique study number to each patient indicating which study group she is allocated to. Result of the randomization will be delivered to the patient by the project nurse and potential disappointment will be handles at this point, and information regarding optional counseling provided by the Danish Cancer Society will also be given.

Intervention group MBSR will be delivered in groups of maximum 20 participants. The course will follow an 8 week schedule with 2-2½ hour sessions each week and instruction to practice 45 minutes daily at home. Upon conclusion of the course each group will participate in a full-day course (8 hours). The courses will be delivered by a manual (including audio CDs) developed by Antonia Sumbundu (see attached file). The group must meet in a quiet room large enough to room 20 persons lying down, as well as mats, carpets and chairs. The courses will be delivered in locations not affiliated with a hospital.

Control group The control group will receive treatment as usual and thus follow the standard control program applied by the surgical department.

* Questionnaire Prior to randomization and as follow-up after 6 and 12 months both study groups will be mailed questionnaires containing validated psychometric
* Hospital charts Descriptions of breast cancer operation, pathology of tumor as well as day to day entries will be collected.
* Administrative registries Data regarding comorbidity of all eligible patients will be collected in National Patient Registry and Central Psychiatric Registry upon finalization of the project.
* Qualitative outcomes Data collected by standardized self-report instruments will be supplemented by qualitative interviews inviting the intervention group participants to present themselves by giving an account of the treatment and a personal evaluation of the potential benefit.

Analysis

* Quantitative data Data will be stores in a database at the institute. Logistic regression analysis will be applied to evaluate which background variables effects participation. Analysis of outcomes will be conducted by applying multiple regressions at each time point. For simultaneous analysis of all follow-up times a linear mixed model with random effects of persons will be fitted. Outcomes as relapse and death among intervention group in comparison to both control group and non-participants will be analyzed by use of Cox regression model, controlling for the effect of biological and demographic variables. Analysis will be conducted under supervision of a senior statistician at the Department of Statistics and Epidemiology at the Institute.
* Qualitative data Based on the qualitative interviews a set of data-driven categories will be developed. These categories will be quantitatively evaluated. The transcript of the patient's self-presentation (approximately 2 pages) will be analyzed by use of qualitative methods, allowing for grouping of content categories as expressed by the patients. Statistical analysis will be applied to evaluate these categories.

Ethics Application of permission to conduct the study will be submitted to the The National Committee on Health Research Ethics and to the Danish Data Protection Agency. In information to patients regarding the study it will be stressed that participation is voluntary and that patients withdraw without any explanation at any time, and that withdrawal will have no influence on treatments delivered. Both written and oral consent must be given prior to participation. A short report will be mailed to all participants upon conclusion of the study. Vital status of participants will be checked in Central Persons Registry prior to any sending of study questionnaire. Data kept in the study database will be encrypted ensuring that only authorized scientific staff will be able to identify individuals. The encryption code will be kept by study manager. Results will be reported as tables and figures hindering identification of individuals. Also in the reporting of qualitative data will the quoted participants be kept anonymous.

Reference List

1. Ross L, Boesen E, Dalton S, Johansen C. Mind and cancer: does psychological intervention improve suvival and psychological well-being? European Journal of Cancer 2001.
2. Ott MJ, Norris RL, Bauer-Wu SM. Mindfulness meditation for oncology patients: a discussion and critical review. Integr Cancer Ther 2006; 5(2):98-108.
3. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life. J Clin Oncol 2000; 18(4):743.
4. Bower JE, Ganz PA, Desmond KA et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 2006; 106(4):751-758.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Psychosexual Consequences of Risk-reducing Salpingo-oophorectomy	NCT02372864	Ovarian Cancer	Mindfulness bas...	-	University Medical Center Groningen
Mindfulness and Cancer Mamma - Clinical Trial MBSR Among Women Operated for Breast Cancer	NCT00990977	Breast Cancer	mindfulness bas...	18 Years - 75 Years	Danish Cancer Society

Spots Global Cancer Trial Database for mindfulness based stress reduction (mbsr)