Comparable Effects of Lanreotide Autogel and Octreotide LAR on GH, IGF-I Levels and Patient Satisfaction
Condition: Acromegaly
MeSH terms: Acromegaly
Study type: Interventional
Phase: Phase 4

Summary: 
      The morbidity and the mortality in acromegalic patients closely correspond to growth hormone
      (GH) levels and therefore efficient long-term treatment is important.

      Neurosurgery is the first choice of treatment in acromegalic patients. Surgery normalizes GH
      levels in about 80% of patients with microadenomas, but less than 50 % of patients with
      macroadenomas respond sufficiently to surgery alone. In most patients, additional medical
      therapy is therefore needed.

      Somatostatin analogues have successfully been used in treatment of acromegaly if surgery or
      radiotherapy can not lead to normal GH and IGF-I levels. Lanreotide Autogel (LAN) is a new
      formulation of lanreotide consisting of a prolonged release aqueous formulation, which can be
      injected intramuscularly or deep subcutaneously once every 28 days.

      Aim

      The aim of the present study was to compare the efficacy of OCT and LAN in obtaining GH and
      IGF-I levels according to the 2000 Consensus. Furthermore, we wanted to evaluate which
      treatment modality resulted in the lowest possible IGF-I and GH levels and the highest
      patient satisfaction.
    

Detailed description: 
      Introduction The morbidity and the mortality in acromegalic patients closely correspond to
      growth hormone (GH) levels and therefore efficient long-term treatment is important (1).

      Neurosurgery is the first choice of treatment in acromegalic patients. Surgery normalizes GH
      levels in about 80% of patients with microadenomas, but less than 50 % of patients with
      macroadenomas respond sufficiently to surgery alone (1). In most patients, additional medical
      therapy is therefore needed.

      Somatostatin analogues have successfully been used in treatment of acromegaly if surgery or
      radiotherapy can not lead to normal GH and IGF-I levels (2, 3, 4, 5). Lanreotide Autogel
      (LAN) is a new formulation of lanreotide consisting of a prolonged release aqueous
      formulation, which can be injected intramuscularly or deep subcutaneously once every 28 days.

      Aim The aim of the present study was to compare the efficacy of OCT and LAN in obtaining GH
      and IGF-I levels according to the 2000 Consensus. Furthermore, we wanted to evaluate which
      treatment modality resulted in the lowest possible IGF-I and GH levels and the highest
      patient satisfaction.

      Inclusion criteria

        -  all the patients which receive octreotide LAR can be included;

        -  new diagnosed patients with clinical and biochemical acromegaly , if medicine therapy is
           indicated;

        -  as long as they do not fit in the exclusion criteria. Exclusion criteria

        -  which had not given their consent after they received standard information about the
           study;

        -  current malign disease;

        -  somatostatin analogues intolerance;

        -  elevation of lever enzymes;

        -  pregnancy.

      Design The study is designed as a randomized cross-over trial. Patients will be randomized to
      receive either OCT or LAN for 6 months and will be then changed to the opposite therapy for 6
      months without interruption between the two therapies Both OCT and LAN will be administered
      once every 28 days. OCT will be given intramuscularly and LAN deep subcutaneously by the
      patients' general practitioner or by a study nurse. At times 0, 4, 6, 10, and 12 months, the
      patients will be attended for clinical evaluation, at the department of Endocrinology, Odense
      University Hospital.

      Patients previously treated with OCT will receive unchanged doses of OCT during the study
      period and OCT dose will use to calculate LAN doses. The administered OCT dose will be
      determined as the dose necessary to obtain normal IGF-I levels and/or GH<1mU/l (<0.4 μg/ l)
      or alternatively the highest tolerated dose.

      The LAN doses will be calculated using the OCT doses as follows: 10 mg OCT ≈ 60 mg LAN; 20 mg
      OCT ≈ 90 mg LAN; 30 mg OCT ≈ 120 mg LAN.

      Evaluation program (at 0, 4, 6, 10, 12 months) Clinical evaluation: weight, blood pressure,
      inspection of the injection site and evaluation of possible side effects.

      Analyses: GH and IGF-I, prolactin, thyroid hormone, oestrogen, testosterone, LH, and FSH,
      fasting plasma glucose and glycosylated hemoglobin, liver enzymes levels.

      The study will be supported by Beaufor Ipsen Industry and further technical assistance will
      be supplied by Endocrinology Department, Odense University Hospital.

      References

        1. Giustina, A., Barkan, A., Casanueva, F. F., Cavagnini, F., Frohman, L., Ho, K.,
           Veldhuis, J., Wass, J., Von, Werder K., and Melmed, S. Criteria for cure of acromegaly:
           a consensus statement.J.Clin.Endocrinol.Metab 2000 85 526-529

        2. Chanson, P. Somatostatin analogs in the treatment of acromegaly: the choice is now
           possible.Eur.J.Endocrinol. 2000 143 573-575

        3. Cozzi, R., Dallabonzana, D., Attanasio, R., Barausse, M., and Oppizzi, G. A comparison
           between octreotide-LAR and lanreotide-SR in the chronic treatment of
           acromegaly.Eur.J.Endocrinol. 1999 141 267-271

        4. Turner, H. E., Vadivale, A., Keenan, J., and Wass, J. A. A comparison of lanreotide and
           octreotide LAR for treatment of acromegaly.Clin.Endocrinol.(Oxf) 1999 51 275-280

        5. Verhelst, J. A., Pedroncelli, A. M., Abs, R., Montini, M., Vandeweghe, M. V., Albani,
           G., Maiter, D., Pagani, M. D., Legros, J. J., Gianola, D., Bex, M., Poppe, K., Mockel,
           J., and Pagani, G. Slow-release lanreotide in the treatment of acromegaly: a study in 66
           patients.Eur.J.Endocrinol. 2000 143 577-584
    

Intervention name(s): Lanreotide Autogel and Octreotide LAR
Intervention type(s): Drug
Intervention MeSH terms: Octreotide; Lanreotide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acromegaly; somatostatin analogues; lanreotide; octreotide; GH; IGF-I; injection site