Detailed Description:
This prospective observational study is designed to evaluate the safety and preliminary
efficacy of intracavernosal injections of autologous adipose tissue-derived stem cells
(ADSCs) or stem cell-derived exosomes for treating erectile dysfunction (ED) in men
unresponsive to conventional therapies, such as phosphodiesterase type 5 (PDE-5)
inhibitors. The primary focus will be on improvements in erectile function, as measured
by changes in the International Index of Erectile Function (IIEF) score. Additionally,
the study will assess penile hemodynamics, monitor adverse events, and explore biomarkers
that may predict therapeutic outcomes.
Background and Rationale:
Erectile dysfunction affects a significant proportion of the male population,
particularly with advancing age, and can result from various causes, including vascular,
neurogenic, and psychogenic factors. Current standard treatments, such as PDE-5
inhibitors, are effective for many, but a substantial subset of patients-especially those
with underlying vascular or nerve-related pathologies-experience inadequate therapeutic
responses.
Regenerative medicine has emerged as a promising approach for addressing ED through
tissue repair and vascular regeneration. Both ADSCs and stem cell-derived exosomes are
potential therapies due to their ability to promote angiogenesis, tissue regeneration,
and anti-inflammatory effects. ADSCs can be harvested from the patient's adipose tissue,
minimizing the risk of immunogenicity or rejection. Exosomes derived from stem cells, on
the other hand, offer a cell-free approach, delivering growth factors and signaling
molecules to the target tissues. Preclinical studies have demonstrated the potential of
these therapies to restore erectile function through tissue remodeling and enhanced
penile blood flow following intracavernosal injection.
Primary Objective:
To evaluate the safety and efficacy of intracavernosal ADSC or stem cell-derived exosome
injections in improving erectile function, as determined by changes in the IIEF score
from baseline through subsequent follow-ups. The IIEF is a validated, comprehensive
questionnaire used to assess erectile function and sexual satisfaction.
Secondary Objectives:
Penile Hemodynamics: Doppler ultrasound will evaluate changes in penile blood flow
post-treatment, providing insight into the vascular effects of the therapies.
Long-Term Effects: Follow-up visits at 3, 6, 9, and 12 months will include IIEF scoring,
Doppler ultrasound assessments, and patient-reported outcomes to evaluate the durability
of treatment effects.
Safety and Adverse Events: All potential adverse events, including injection-site
reactions and systemic complications, will be closely monitored and documented throughout
the study.
Biomarker Exploration: Exploratory analyses will aim to identify biomarkers, including
vascular and tissue-specific markers, which may predict patient response to the
treatment.
Study Design:
This open-label, single-arm, pilot observational study will serve as a preliminary
investigation of ADSC or stem cell-derived exosome therapy in ED, providing foundational
data on their feasibility and safety. As a prospective observational study, the emphasis
will be on safety and gathering initial efficacy data rather than delivering definitive
conclusions.
Study Population:
The study will enroll 30 men aged 30 to 75 years with a diagnosis of mild to moderate
erectile dysfunction who have failed or experienced suboptimal responses to PDE-5
inhibitors. Participants will be recruited from Dr. Ranjith Ramasamy's clinic, where they
are receiving care for ED. Inclusion and exclusion criteria have been carefully designed
to select participants who are most likely to benefit from these therapies and ensure
patient safety.
Sample Size Rationale:
A sample size of 30 was chosen based on the exploratory nature of the study. The primary
goal is to assess feasibility, safety, and preliminary efficacy while providing
sufficient data to inform the design of future, more extensive studies. Recruitment of 30
participants is feasible within the clinic's patient population over the planned two-year
period.
Study Procedures:
Informed Consent: Participants will be fully informed about the study, including its
risks and benefits, and will provide written consent prior to enrollment.
Baseline Assessments: Baseline data, including IIEF scores, penile Doppler ultrasound,
and blood tests, will be collected to assess pre-treatment erectile function and overall
health.
Therapeutic Administration:
For ADSCs: ADSCs will be isolated from autologous adipose tissue harvested via minimally
invasive liposuction. The cells will be processed and prepared for direct injection into
the corpus cavernosum. A tourniquet will be placed for 15 minutes around the base of the
penis after the injection to minimize systemic dispersion.
For Exosomes: Exosomes derived from stem cells will be isolated and purified, then
injected intracavernosally using a similar protocol.
Follow-Up Monitoring: Participants will be monitored for immediate post-injection
reactions and at regular intervals (3, 6, 9, and 12 months) for changes in erectile
function (IIEF), penile hemodynamics (Doppler ultrasound), and adverse events.
Exploratory biomarker analysis will also be conducted.
Data Collection and Analysis:
Data will be analyzed to evaluate primary and secondary outcomes. IIEF score changes will
be the primary efficacy measure, while penile hemodynamics and adverse event rates will
be assessed for safety. Exploratory analyses will investigate the correlation between
biomarkers and clinical outcomes, providing insights into potential predictors of
treatment response.
Ethical Considerations:
This study will adhere to ethical standards for clinical research. Informed consent will
be obtained from all participants, and the protocol will be reviewed and approved by an
ethics committee. Participants will have the right to withdraw at any point, and their
standard medical care will not be affected by their participation.
Expected Outcomes:
The study aims to provide early evidence on the safety and potential efficacy of ADSC or
stem cell-derived exosome therapy for ED. If successful, participants are expected to
show improvements in erectile function with minimal adverse events. The findings from
this study will inform larger, more definitive trials and contribute to the development
of novel regenerative therapies for erectile dysfunction.