Sandostatin therapy in sarcoidosis

The association between somatostatin receptor activity and octreotide uptake on
SRS in SA has been described in various reports. SA remains a rare, systemic
disease with granulomatous inflammation in various parts of the body. In many
cases there is no need for treatment and naturally recovery is seen. However, a
subgroup of patients suffer from a chronically active and complicated form of
SA that require therapy. These chronic patients that are regularly seen in the
Erasmus MC as it is a tertiary referral and *sarcoidosis centre*. First line
therapy contains corticosteroids. However, these agents can have serious side
effects, on short term it can cause diabetes, but also long-term complications
such as osteoporosis are frequently seen. Also, patients can be refractory to
this treatment and need more aggressive therapy. The introduction of anti-TNF *
agents looked promising a few years ago. Patients can also be non-responders
and form auto-antibodies or have allergic reactions to it. Because of the high
costs involving this treatment, implementation is limited and still is reserved
for a subgroup of patients with SA. Therefore, there is still a need for more
therapeutic options. Treatment with SST is worth studying for several reasons.
1.In some patients with active sarcoidosis no effect of conventional therapy
is seen or the severity of treatment does not outweigh the side effects. 2.
Sarcoidosis expresses somatostatin receptors that are represented in SRS and
treatment with octreotide is proven successful in other somatostatin positive
disorders. 3. Somatostatin analogues are proven safe and have relatively few
side effects.

Primary Objective: To evaluate efficacy of SST looking at the change in uptake
on SRS in a subset of chronically active patients in which intensification of
corticosteroid therapy is not indicated. .

Secondary Objective(s): To study the composite clinical score using the
following parameters: blood test (ESR, CRP, full blood count, lysozyme, ACE,
25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, sIL-2R), quality of life
(RAND-36) and when applicable lung function test (FVC, DLCO) and skin
evaluation.

The current study is a nonrandomized, open label trial. The intention is to
treat 20 patients with biopsy-proven symptomatic, chronic (>3 years) and stable
SA. All patients have a need for maintenance therapy, but not for intensifying
therapy towards preventing organ damage.

All 20 patients receive an injection of 20 mg of sandostatin for six months,
every month. Before start of study and at two weeks and three and six, nine and
twelve months, patients will visit the outpatient clinic for evaluation,
measurements of endpoints and collection of adverse events. In case of
unsatisfactory response to treatment, SST will be uptitrated to 30 mg
injections at month 3.

Inclusion of patients will be started from April 2014 until April 2015.
Liverenzymes, TSH and glucose level and ECG will be evaluated before start of
treatment and at week two and three and six, nine and twelve months into the
program when blood is drawn to measure endpoints. After six injections,
treatment is stopped. It is thought that during treatment with SST, SRS will
not be reliable as an assessment tool as the receptors are blocked For this
reason SRS will be conducted at month nine when patients are free of SST
treatment for three months. SST will be restarted in case of a good clinical
response and relapse after cessation of treatment.
In order to evaluate the efficacy of SST, patients will be actively followed
during therapy and in the six months following treatment. Then, statistical
analysis and writing of the scientific article will take place.

Treatment with Sandostatin LAR 20 mg injections every months for six months.

Patients with SA may suffer from various symptoms, some more severe than
others. Treatment remains difficult in a group of SA patients, specifically in
chronic disease. SST may potentially be a target for therapy as patients
express somatostatin on SRS. Therefore, the efficacy of SST is studied in
chronic, symptomatic SA patients. Patients may directly benefit from this
trial. Adverse events are well documented and will be closely monitored. SST is
considered a safe agent and is studied and used for many years. Patients with
SA visit the outpatient clinic on a regular basis, every three months. For this
trial, patients will visit the clinic one extra time, at two weeks into the
study. The extra volume of bloodwithdrawal and extra pulmonary function test is
considered a very light burden. SRS is a moderate burden considering the use of
laxatives and duration of the scan, however it has an acceptable radiation
load.