Improving Erectile Function and Quality of Life After Prostate Cancer Treatment

Erectile dysfunction (ED) is a common side effect of prostate cancer treatment. Existing
medical treatment focuses on early penile rehabilitation, aiming to prevent penile shrinkage
and preserve nerves and smooth muscles to facilitate erection return. It typically includes
administration of phosphodiesterase type 5 inhibitor (PDE-5), application of vacuum
constriction devices (VCD) or intracavernous injection immediately after prostate cancer
treatment.

To evaluate the proposed intervention, a randomized, controlled longitudinal clinical trial
will be conducted to examine the effect of this cognitive-behavioral intervention on
early-stage prostate cancer patients with ED and their partners. The proposed study includes
a pilot study, a randomized clinical trial (the main study) and data analysis. The study
duration for main study participants is 10 months including one month of recruitment and
baseline assessment, six months of intervention, and three months of follow-up. The study
duration for pilot study participants is 7 months including one month of recruitment and
baseline assessment plus six months of intervention.

The Pilot Study A pilot study will be conducted to develop and test the proposed study
intervention over 12 months. The pilot study will recruit 36 early-stage prostate cancer
patients and their partners. The 36 couples will be randomly assigned to three study arms:
(1) standard medical treatment of ED (MED); (2) standard medical treatment of ED plus
cognitive-behavioral intervention (MED+CBI); and (3) usual care (UC) in which the study
participants will not receive any study intervention, but will continue with standard care
that allows patient's request for ED treatment. The purpose to include the usual care group
is to collect preliminary data to aid the estimation of intervention effect size, statistic
power and sample size, and to compare the intervention outcome with the real world scenario
in order to provide the justification for the inclusion or exclusion of the usual care arm in
the main study. The pilot study participants will be assessed twice at baseline (T1) and 7
months (T2) only. Doppler Ultrasound of the penis will be performed at T1 and T2 to examine
changes in the volume of penile blood flow in patients. Subjects are allowed to opt out of
the Doppler Ultrasound test, because this pilot data is exploratory and five or more
ultrasound tests per group are sufficient. Collecting and analyzing blood samples will be
performed at T1 and T2 and subjects are allowed to opt out of this test as well. The blood
sample will be collected in order to test transforming growth factor beta-1 (TGF-ß1) and to
assess its relation to erectile function. The result will allow us to evaluate the
intervention impact at molecular level and formulate a best possible intervention to ED.

The Main Study During a 4-year clinical trial study, 144 early-stage prostate cancer patients
along with their partners will be randomly assigned to two study arms: (1) standard medical
treatment of ED (MED) and (2) standard medical treatment of ED plus cognitive-behavioral
intervention (MED+CBI). The MED includes administration of sildenafil citrate (Viagra) and/or
vacuum constriction devices (pump). The MED+CBI entails six in-person sessions and five
telephone follow-ups over six months. The patients will be assessed on erectile function
(EF), quality of life (QOL) and mood at baseline (T1), 7 months (T2) and 10 months (T3). The
partners will be assessed on QOL and mood at T1, T2 and T3. Doppler Ultrasound of the penis
will be performed at T1 and T2 to examine changes in the volume of penile blood flow among 50
patients who will be consecutively selected from the two study groups, with 25 per study arm.

The long-term primary goals of the study are to:

1. Assess the effect of the new treatment on erection function, quality of life, and mood.

2. Assess the treatment compliance and frequency of sexual activity of the new treatment.

3. Investigate the mechanism in which the new treatment works.

The long-term secondary goals of the study are to:

1. Assess the effect of the new treatment on the quality of life and mood of the patient's
partner.

2. Assess the changes in the volume of penile blood flow due to study treatments.

Inclusion Criteria:

- Stage I, II, and III prostate cancer

- Having completed definite treatment of localized prostate cancer (surgery or
radiation);

- Presence of erectile dysfunction symptoms;

- Have a stable partner for six months who is willing to participate;

- Sexually active prior to cancer treatment (≥17 on the Sexual Health Inventory For Men―
("SHIM")).

- Prostatectomy with or without radiation for the pilot study patients only.

Exclusion Criteria:

- Receiving hormonal treatment;

- Cognitive impairment (≥5 on the Short Portable Mental Status Questionnaire (SPMSQ));

- Severe marital maladjustment that prevents a patient from benefiting from the proposed
intervention (<85 on the Locke-Wallace Marital Adjustment Test);

- Taking nitrates of any kind;

- Congenital bleeding disorder or predisposition to priapism that is contraindicative to
VCD use;

- Having untreated clinical depression and other psychotic mental disorders (e.g.,
bipolar, schizophrenia) (≥27 on the Center for Epidemiological Studies Depression
Scale (CES-D)).

- Patients taking any potent inhibitor of cytochrome P450 3A4 (e.g., ketoconazole,
itraconazole, erythromycin, etc).

- Patients taking concomitant alpha-adrenergic blocking agents.

- Patients with a clinically significant abnormality on screening ECG (taken within 12
weeks) that in the opinion of the investigator/co-investigator may increase the
patient's cardiovascular risk in this study.

- Patients with a history of left ventricular outflow obstruction (e.g., aortic
stenosis, idiopathic hypertrophic subaortic stenosis).

- Patients with a history of severely impaired autonomic control of blood pressure.

- Patients with resting hypotension (BP < 90/50 mm Hg), or resting hypertension (BP >
170/110 mm Hg) at Screening.

- Patients with known hypersensitivity to Sildenafil or other ingredients of Sildenafil.

- Patients with retinitis pigmentosa.

- Patients with active peptic ulceration.

- Patients who have previously experienced non-arteritic ischemic optic neuropathy
(NAION).

- Patients taking other phosphodiesterase Type 5 (PDE5) inhibitors.

- Patients taking Coumadin, Pradaxa or other blood thinner drugs.