Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05222282 |
| Other study ID # |
Sexual Health |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2022 |
| Est. completion date |
January 1, 2025 |
Study information
| Verified date |
September 2023 |
| Source |
Rigshospitalet, Denmark |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Sexual wellbeing is an integral component of psychosocial and physical wellbeing.
Cancer-related symptoms, treatment side-effects and psychosocial distress have significant
impact on sexual well-being and sexual health. Within the framework of sexual wellbeing,
sexual function is defined by a capacity to fully engage in all phases of the human sexual
response cycle. Thus, sexual dysfunction is characterized by a disruption in one or more
elements of the response cycle. Previous research shows that patients with hematologic
malignancies and specifically patients following stem cell transplantation experience a high
symptom burden and distinct genital alterations, and therefore in increased risk of sexual
dysfunction. In spite of growing evidence documenting high prevalence of sexual dysfunction
in cancer patients, patients with hematologic malignancies are underrepresented in clinical
trials investigating their sexual health. This study aims to examine the sexual health in
patients across hematologic malignancies in Denmark, and to investigate feasiblity and effect
of a randomized multimodal intervention by providing nurse-led sexual consultations and
physician-led preventive genital examinations, to enhance sexual function and early
recognition of gential graft versus host disease in adult patients following hematopoietic
stem cell transplantation. Finally, the study aims to explore perspectives and experiences of
patients following this multimodal intervention. This knowledge will entail new opportunities
to detect subgroups of patients with distinct risk of sexual dysfunction, and potentially
lead to targeted interventions in clinical practice toward this specific population. Moreover
this will provide evidence with high methodological rigor and potentially strengthen the
possibilities for evidence-based decision making in Denmark regarding preventive gential
examinations during follow-up in patients following stem cell transplant.
Description:
1. Introduction As the survival rates for hematologic malignancies improves there is
subsequently an increased need for addressing long-term complications. The evidence
highlight that patients experience a high symptom burden including sexual dysfunction,
and therefore in increased risk of decreased sexual health. Sexual health is a state of
physical, mental and social well-being in relation to sexuality, and can reduce the
emotional distress and improve psychosocial response to a cancer diagnosis and
complications following treatment. Still, this population is underrepresented in
clinical trials investigating their sexual health. It is therefore essential to include
them in future clinical trials in order to have a comprehensive view of their condition
of sexual health and sexual function. This knowledge will entail new opportunities to
detect subgroups of patients with distinct risk of sexual dysfunction, and this will
potentially lead to targeted interventions in clinical practice toward this specific
population.
In patients with hematologic malignancies undergoing hematopoietic stem cell
transplantation (HSCT) sexual dysfunction is one of the most frequent long-term issues.
Sexual dysfunction include decreased libido, vaginal alterations, erectile and
ejaculatory dysfunction, dysfunction in sexual hormones, dyspareunia and infertility.
Specifically, an immunologic reaction in the skin tissue called genital graft versus
host disease (GHVD), is a major determinant of sexual dysfunction in this population.
Genital GVHD can lead to vaginal stenosis, scar tissue and adhesions in blood vessels,
rash and increased sensitivity in the skin of the genitals. Despite increasing evidence
on the clinical manifestations it is still an underrecognized and underestimated
complication of HCST in clinical practice due to the nonspecific nature of presenting
symptoms and low awareness of the condition. In a previous systematic review, the
investigators concluded that multiple aspects of sexuality were affected following
treatment with HSCT, and the impact and ethology of these sexual alterations were
different between genders. Therefore, the investigators investigated the impact of HSCT
on sexuality in a resent longitudinal survey. The results showed a significant decline
in overall sexual function in both men and women. Still, most studies have solely
investigated female genital GVHD, in small populations and only few have included
evaluations of sexual function prior to HSCT. No previous studies have investigated the
effect of a multimodal intervention specifically focused on evaluation of sexual
function through nurse-led sexual consultations and early recognition of genital GVHD in
patients during treatment with HSCT. Thus, further recognition of sexual symptoms and
regular follow-up can possibly help to improve the detection and facilitate early
treatment of sexual complications including genital GVHD. This will help our
understanding in the development of systematic strategies to prevent or treat its
long-term effects.
2. Hypotheses
This study is based on the following hypothesis or assumptions:
Study 1
• The investigators hypothesize that patients with hematologic malignancies report
impaired sexual function, and that sexual dysfunction are associated with high symptom
burden, sexual distress, reduced quality of life and increased anxiety and depression.
Study 2
• The investigators hypothesize that a multimodal intervention with nurse-led sexual
counseling and systematic gential evaluations is feasible and will enhance sexual
function in patients undergoing HSCT
3. Aim The overall aim of this study is to investigate sexual health in patients treated
for a hematologic malignancy, and to generate research-based knowledge on the feasiblity
and effect of a multimodal intervention with nurse-led sexual counseling and systematic
genital evaluation on sexual function in patients during their treatment with HSCT.
The specific aims of the studies are:
Study 1
• To examine the sexual health in patients across hematologic malignancies in Denmark,
and to examine the prevalence and factors associated with sexual dysfunction in this
population.
Study 2
• To investigate feasibility and effect of a randomized multimodal intervention with
nurse-led sexual counseling and systematic genital evaluation on enhancing sexual
function in patients undergoing HSCT.
4. Study description study 1 4.1 Aim To examine the sexual health in patients across
hematologic malignancies in Denmark, and to examine the prevalence and factors
associated with sexual dysfunction in this population.
4.2 Design and methods This study is an explorative cross-sectional national study
examining sexual health across different haematological malignant diseases in Denmark.
4.3 Participants Participants with haematological malignant diseases specifically acute
myeloid leukemia (AML), acute lymphatic leukemia (ALL), chronic lymphatic leukemia
(CLL), chronic myeloid leukemia (CML), multiple myeloma, non-Hodgkin lymphoma, Hodgkin
lymphoma, are eligible if > 18 years with time post diagnosis > 3 month up to 10 years.
Participants are excluded if they are unable to read or speak Danish or have a cognitive
disorder.
4.4 Recruitment and procedure Eligible participants will be identified through the
National Patient Register. Then, the Danish Health Data Authority will be applied to
extract a representative sample from the full potential eligible participants. This
sample will be based on statistical measurements to achieve high statistical power.
Eligible participants will receive information about the study, provide written informed
consent and receive the questionnaires electronically through e-boks.
4.5 Data collection
Participant and disease characteristics will be obtained from the participants. These
will include age, gender, marital status, education, employment status, disease type and
status, type and intensity of treatment received, and treated hospital. The
patient-reported outcome measure (PROM) include:
- Sexual health will be assessed by the Female Sexual Function Index (FSFI) in female
participants. FSFI is a brief 19-item self-report measure of female sexual function
that provides scores on six domains: desire, arousal, lubrication, orgasm,
satisfaction and pai. In male participants, sexual health will be assessed by The
International Index of Erectile Function Questionnaire (IIEF). IIEF is a brief
15-item widely used multi-dimensional self-report instrument for evaluation of male
sexual function that proves scores in five domains: erectile function, orgasmic
function, sexual desire, intercourse satisfaction, and overall satisfaction.
- Sexual distress will be assessed by the Female Sexual Distress Scale - Revised
(FSDS-R). FSDS-R is a 13 item measure assess sexual distress specifically related
to low sexual desire. The scale has been developed for use in female patients but
have recently been validated in male patients with excellent internal consistency
and test-retest reliabilities.
- Quality of life will be assessed by The European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire (EORTC-C30). EORTC-C30 is a 30
item multi-dimensional quality of life measure designed for use in cancer patients.
- Symptom burden will be assessed with M.D. Anderson Symptom Inventory (MDASI) which
is a 19 item measure and assesses the severity of 13 symptoms and their impact in
cancer patients.
- Psychological well-being will be assessed and measured by using the Hospital
Anxiety and Depression Scale (HADS), which is a brief 14-item self-report measure
of anxiety and depression.
4.6 Analysis Statistical analysis will be conducted using IBM SPSS Statistics for
Windows, version 25. Throughout, two-sided P-values <0.05 confidence intervals are
considered indicators of statistical significance.
5. Study description study 2 5.1. Aim To investigate feasibility and effect of a randomized
multimodal intervention with nurse-led sexual counseling and systematic gential
evaluation on enhancing sexual function in patients undergoing HSCT.
5.2 Design and methods This study is a prospective two-arms randomized controlled trial
to assess the feasibility and effect of a multimodal nonpharmacological intervention to
address sexual health in patients undergoing HSCT.
5.3 Participants Patients (age>18 years) with a hematologic malignancy who is planned to
undergo an HSCT, who provide informed written consent and can understand, speak and read
Danish are eligible to participate. The exclusion criteria include patients with
dementia, psychotic disorders, or other cognitive diseases or conditions that hinder
participation.
5.4 Recruitment and procedure Patients will be recruited from the Department of
Hematology, Rigshospitalet. Eligible participants receive oral and written project
information from primary research investigator (KHN) during their preexamination week
prior to HSCT. Patients will be informed about the trial, perceived benefits, risks, and
safety precautions, and about their personal rights in entering the trial. Study
participants who complete baseline questionnaires are then randomized, and participants
in the intervention group will be scheduled for their first assessment.
Randomization and blinding Patients included in the study will be randomized 1:1 ratio
to either the intervention group or control group (usual care) by KHN. Randomization and
stratification (age, diagnosis) will be performed through the randomization module in
Redcap. Because it is not feasible, the primary investigator and the patient will not be
blinded to group allocation. However, to reduce the risk of detection bias, the
investigator will be blinded to group allocation during data entry. Moreover, the
statistician will be blinded to allocation during data analysis. The identity of each
patient will be masked and can only be re-identified using a separately kept key file.
Usual care Patients allocated to control group will receive usual care which include
genital evaluation during their preexamination week prior to HSCT. During the treatment
trajectory genital examination is conducted when genital symptoms are reported either by
the health care provider or the patient. Patients in the control arm will receive a
final assessment with genital evaluation and nurse-led sexual counseling. Data
collection with PROM will be conducted prior to the final genital evaluation and
nurse-led sexual counseling.
5.5 Multimodal Sexual Dysfunction Intervention The intervention consists of nurse-led
sexual counselling and systematic genital evaluation (Figure 1). The intervention begins
during their preexamination week prior to HSCT and the subsequent 18 months.
Nurse-led sexual counseling The intervention entails five nurse-led sexual counseling
sections. Participants will attend their first nurse-led sexual counseling session three
month post HSCT with KHN who is an experienced HSCT nurse. The patients will fill out
the PROMS related to GVHD and sexual function as a screening tool which guide the
counselling session and the subsequent genital evaluation. The counselling consists of
guidance and follow-up on relevant issues related to disease and treatment sexual
complications including genital GVHD. The first intervention visit will be conducted
in-person in the outpatient clinic. Subsequent visits can be conducted in-person or over
the telephone. Participants with complex sexual health concerns will be referred to the
Sexual Health Clinic at Rigshospitalet for further evaluation.
Genital evaluation Female patients will have a baseline gynecological review with a
specialist experienced in post-transplant gynecological care during their preexamination
week. During the intervention the patients will have 5 preventive control visits which
include a through genital examination and evaluation including menopausal symptoms,
genital GVH, and genital tract malignancies.
Male patients will have a baseline urological review with a specialist experienced in
post-transplant urological care. During the intervention the patients will have 5
preventive control visits, and the consultation will include a through genital
examination and evaluation including genital GVHD.
5.6 Data collection
Participant and disease characteristics will be obtained from the participants. These
will include age, gender, marital status, education, employment status, disease type and
status, type and intensity of treatment. The patient-reported outcome measure (PROM)
include:
Primary outcome
• The primary outcome is sexual function which will be assessed by FSFI in female
participants, and in male participants by IIEF.
Secondary outcomes
- Feasibility of the intervention will be evaluated as acceptability, practicability,
integration, adherence to protocol, resource utilization and safety.
- Sexual distress will be assessed by the FSDS-R.
- Symptoms of genital GVHD will be assessed by specially developed questions based on
clinical and experienced manifestations of genital GVHD.
- Symptoms of GVHD in other organs will be assessed by the chronic GVHD symptom
scale. The scale contains 30 items in 7 subscales (skin, eye, mouth, lung,
nutrition, energy, and psychological), and patients report their level of symptom
over the past month.
- Quality of life will be assessed by EORTC-C30.
- Symptom burden will be assessed with MDASI. 5.7 Analysis Study feasibility
parameters will be described and analyzed using descriptive statistics. The
demographic and clinical characteristics of participants will be summarized in
percentages for categorical variables and mean (SD) for noncategorical variables.
Mean score will be calculated for each group and compared using student´s t-test.
The domains of questionnaires will be calculated for each group and compared using
Wilcoxon´s rank-sum test. Throughout, two-sided P-values <0.05 confidence intervals
are considered indicators of statistical significance. Statistical analysis will be
conducted using IBM SPSS Statistics for Windows, version 25.
Sample size
- In female patients, assuming a difference of size 2.1 for the primary outcome
(FSFI) between intervention and control group and a standard deviation of 3.86
points for the primary outcome within each group and with a two-sample t-test with
a power of 80 % to detect a significant difference at level 0.05 if 55 patients are
included in each treatment arm. To account for an expected dropout rate of 20 % the
investigators decided to increase this number to a group size of 66.
- In male patients, assuming a difference of size 5.0 for the primary outcome (IIEF)
between intervention and control group and a standard deviation of 9.3 points for
the primary outcome within each group and with a two-sample t-test with a power of
80 % to detect a significant difference at level 0.05 if 56 patients are included
in each treatment ar. To account for an expected dropout rate of 20 % the
investigators decided to increase this number to a group size of 67.
There is yearly around 95 patients receiving HSCT at Department of Hematology,
Rigshospitalet. Based on this and an expected acceptance of 75%, the investigators aim
to include 133 patients in each arm of the study, and therefore the project is estimated
to run for 42 months, starting fall 2021.
6. Ethical considerations This study will be registered with the Danish Protection Agency
and Clinical Trials. Each participant will receive written and verbal information on the
study and assurance of confidentiality according to the principles for research stated
in the Helsinki Declaration. Written consent will be obtained from patients
participating at time of recruitment. Awareness of the informant's vulnerability mean
that additional attention will be paid to the voluntariness in their participation, just
as they are given time to debrief and further discuss their experiences.
7. Setting Department of Hematology, Rigshospitalet, Denmark will be Primary sponsor for
this project. KHN will be principal investigator of all studies in collaboration with
the research management group, the national and international research collaborators
(mentors) and clinical collaborators who all have agreed to participate in the study
(Figure 2, Table 1).
