IGF-1 and Bone Loss in Women With Anorexia Nervosa

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01406444
• Collaborator: (none)
• Enrollment: 148
• Location: 1
• Arms: 3
• Duration (Months): 91
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Anorexia nervosa is an eating disorder that can cause thinning of the bones (a decrease in bone density). A significant decrease in bone density is called osteopenia or osteoporosis. Sometimes the loss of bone density can be severe enough to cause breaks and fractures of the bones. It is not known what causes the bones to thin in anorexia nervosa. Women who have this condition often have thin or weak bones that are more likely to break. They also have very low levels of a chemical called IGF-1 in their body. This chemical is very important for increasing bone growth in puberty and for maintaining healthy adult bones. The investigators would like to find out if giving rhIGF-1 followed by risedronate or risedronate alone can lead to an increase in bone formation, bone density, and bone strength in women with anorexia nervosa.

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa; Osteopenia; Osteoporosis	Drug: rhIGF-1; Drug: Risedronate; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: IGF-1 and Bone Loss in Women With Anorexia Nervosa
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: rhIGF-1 followed by Risedronate Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Drug: rhIGF-1; Study participants will be started at a dose of 30 mcg/kg BID and will be titrated.; Other Names: Increlex ; Drug: Risedronate; Risedronate 35mg PO one time weekly; Other Names: Actonel
Active Comparator: Risedronate Risedronate 35mg PO once weekly for 12 months	Drug: Risedronate; Risedronate 35mg PO one time weekly; Other Names: Actonel
Placebo Comparator: Placebo Placebo for 12 months	Drug: Placebo; Placebo injections 30 mcg/kg BID, Placebo tablet PO once weekly

Outcome Measures

Primary Outcome Measures

1. Postero-anterior Spine Bone Mineral Density by DXA [12 Months]

   Postero-anterior spine bone mineral density by dual-energy X-ray absorptiometry

Secondary Outcome Measures

1. Lateral Spine Bone Mineral Density by DXA [12 Months]

   Lateral spine bone mineral density by dual-energy X-ray absorptiometry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-45 years

• AN defined by DSM-IV diagnostic criteria, including weight less than 85% of ideal body weight (restricting or binge/purge type, BMI 15-17.5) OR meet criteria for sub-threshold AN, i.e., all DSM-IV criteria except that patients can have a BMI of <18.5 kg/m2 with or without amenorrhea

• Oral contraceptive use prior to enrollment

• BMD T score < -1.0

• Normal FSH and TSH or free T4

• Normal serum 25-OH vitamin D (>20 ng/mL) and calcium levels

• Ongoing care from a primary care provider

• Agree to use barrier contraception

Exclusion Criteria:

• Any subject with contraindications to risedronate

• Any subject with binge-purge subtype of anorexia nervosa who vomits regularly as their form of purging (vs. those who use laxatives or diuretics) and who have significant periodontal disease, tooth erosion or an invasive dental or periodontal procedure within the previous three months.

• Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's or renal failure

• Any medication known to affect bone metabolism within 3 months of the study, excluding oral contraceptives. Bisphosphonates must have been discontinued for at least one year before participation

• Serum potassium <3.0 meq/L

• Serum ALT >3 times upper limit of normal

• eGFR of less than 30 ml/min

• Pregnant and/or breastfeeding

• Diabetes mellitus

• Active substance abuse, including alcohol

• History of malignancy

• Atraumatic fracture within the prior year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Anne Klibanski, MD, Massachusetts General Hospital
• Study Chair: Erinne Meenaghan, NP, Massachusetts General Hospital
• Study Director: Karen Miller, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - Jan 16, 2019
• Statistical Analysis Plan - Jan 16, 2019

More Information

Publications

None provided.

• Responsible Party: Karen Klahr Miller, MD, Chief, Neuroendocrine Unit, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01406444
• Other Study ID Numbers: 2R01DK052625
• First Posted: Aug 1, 2011
• Last Update Posted: Jul 17, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Karen Klahr Miller, MD, Chief, Neuroendocrine Unit, Massachusetts General Hospital: Anorexia Nervosa; Osteopenia; Osteoporosis; Bone density
• Additional relevant MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Anorexia; Anorexia Nervosa; Risedronic Acid

Study Results

Participant Flow

Pre-assignment Detail	148 subjects were consented and screened, 90 subjects were randomized, and 82 subjects completed the baseline visit. Of the 90 who were randomized, 8 subjects did not attend their scheduled baseline visits and did not receive study medication.

Arm/Group Title	rhIGF-1 Followed by Risedronate	Risedronate	Placebo
Arm/Group Description	Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Risedronate 35mg PO once weekly for 12 months	Placebo for 12 months
Period Title: Overall Study
STARTED	33	33	16
COMPLETED	23	24	14
NOT COMPLETED	10	9	2

Baseline Characteristics

Arm/Group Title	rhIGF-1 Followed by Risedronate	Risedronate	Placebo	Total
Arm/Group Description	Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Risedronate 35mg PO once weekly for 12 months	Placebo for 12 months	Total of all reporting groups
Overall Participants	33	33	16	82
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.9 (6.5)	28.1 (7.1)	25.4 (6.3)	27.5 (6.7)
Sex: Female, Male (Count of Participants)
Female	33 100%	33 100%	16 100%	82 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 3%	0 0%	1 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	30 90.9%	32 97%	14 87.5%	76 92.7%
More than one race	1 3%	0 0%	1 6.3%	2 2.4%
Unknown or Not Reported	2 6.1%	0 0%	1 6.3%	3 3.7%
Body mass index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	18.4 (1.5)	18.4 (2.2)	18.6 (1.7)	18.4 (1.8)
Postero-anterior spine bone mineral density (g/cm2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/cm2]	0.88 (0.12)	0.86 (0.12)	0.88 (0.12)	0.88 (0.12)
Lateral spine bone mineral density (g/cm2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/cm2]	0.67 (0.09)	0.66 (0.09)	0.67 (0.07)	0.67 (0.09)

Outcome Measures

1. Primary Outcome

Title	Postero-anterior Spine Bone Mineral Density by DXA
Description	Postero-anterior spine bone mineral density by dual-energy X-ray absorptiometry
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rhIGF-1 Followed by Risedronate	Risedronate	Placebo
Arm/Group Description	Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Risedronate 35mg PO once weekly for 12 months	Placebo for 12 months
Measure Participants	23	24	14
Least Squares Mean (Standard Error) [g/cm2]	0.891 (0.014)	0.887 (0.014)	0.874 (0.013)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhIGF-1 Followed by Risedronate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Linear random effects model
	Comments

2. Secondary Outcome

Title	Lateral Spine Bone Mineral Density by DXA
Description	Lateral spine bone mineral density by dual-energy X-ray absorptiometry
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rhIGF-1 Followed by Risedronate	Risedronate	Placebo
Arm/Group Description	Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Risedronate 35mg PO once weekly for 12 months	Placebo for 12 months
Measure Participants	23	24	14
Least Squares Mean (Standard Error) [g/cm2]	0.695 (0.012)	0.677 (0.012)	0.666 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhIGF-1 Followed by Risedronate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Linear random effects model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	rhIGF-1 Followed by Risedronate, Risedronate
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Linear random effects model
	Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	rhIGF-1 Followed by Risedronate		Risedronate		Placebo
Arm/Group Description	Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly		Risedronate 35mg PO once weekly for 12 months		Placebo for 12 months
All Cause Mortality
	rhIGF-1 Followed by Risedronate		Risedronate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)		0/16 (0%)
Serious Adverse Events
	rhIGF-1 Followed by Risedronate		Risedronate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	rhIGF-1 Followed by Risedronate		Risedronate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/33 (57.6%)		18/33 (54.5%)		5/16 (31.3%)
Gastrointestinal disorders
Nausea	1/33 (3%)	1	5/33 (15.2%)	14	1/16 (6.3%)	1
Upset Stomach	3/33 (9.1%)	3	1/33 (3%)	1	0/16 (0%)	0
Acid Reflux	4/33 (12.1%)	6	3/33 (9.1%)	4	2/16 (12.5%)	2
Diarrhea	0/33 (0%)	0	2/33 (6.1%)	2	0/16 (0%)	0
Constipation	0/33 (0%)	0	3/33 (9.1%)	3	0/16 (0%)	0
General disorders
Headache	1/33 (3%)	1	1/33 (3%)	1	2/16 (12.5%)	2
Achiness	1/33 (3%)	1	4/33 (12.1%)	5	0/16 (0%)	0
Dizziness	0/33 (0%)	0	0/33 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Injection Site Irritation and/or Bruising	15/33 (45.5%)	24	11/33 (33.3%)	14	2/16 (12.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.